Capsule cures get beta

We’ve learned how to churn out zillions of insulin-producing cells and maybe even guard them from the immune system for a year or two.

The commercial “stem cell clinics” that have popped up across the U.S. like mosquitoes after rain, offering treatments with little clinic evidence, typically begin with the patient’s own cells. But the stem-cell-based therapies that will soon fundamentally change regenerative medicine will come off the shelf. Case in point, the insulin-producing treatments for type 1 diabetes that I’ve just covered in The Scientist, which are headed for the clinic in the next year or two. Scientists are mastering ways to make reasonably functional beta cells in high volume. ViaCyte is readying a new version of its capsule that doesn’t require immunosuppression and expects to resume clinical trials soon. Semma Therapeutics and Sigilon Therapeutics are reporting progress in pre-clinical studies. Fingers crossed here, but definite progress.

Images courtesy Sigilon Therapeutics.

Debugging global health

Why don’t governments more directly sponsor novel antibiotics, as they do vaccines?
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The stories we write today about the threats of antibiotic-resistant bacteria read very much like the ones we wrote 15 years ago. Bacteria evolve more threatening forms, drug companies evolve toward more profitable markets, and we still depend on the invisible hand of the market to fix everything as it does so smoothly in the rest of healthcare. But there’s another option: Bringing national governments and international agencies more directly into full supervision and sponsorships of the drugs, as often is done extremely effectively with vaccines. Why not? Check out this early proposal for “a joint, internationally-funded antimicrobial development institute that would fund permanent staff to take on roles previously assigned to pharmaceutical companies.”

Hot water for fisheries management

As climate change deepens, we’ll need to understand entirely new marine ecosystems.

Here’s the good news: Since 1990, the catch of Maine lobsters has quintupled.

Okay, the rest of the news, as in other stories about climate change, is not so good.

The bumper crops of lobsters apparently have been driven by warming in the Gulf of Maine. Sea surface temperatures have climbed about four times as much in recent decades in the Gulf as in the global ocean average, according to Andrew Pershing, chief scientific officer at the Gulf of Maine Research Institute.

Lobster populations have moved northeast from southern New England waters,  Pershing said, speaking at a Metcalf Institute seminar on climate change held in Cambridge last Saturday. The shift has been a boon for Maine but a bust for fisheries south of Cape Cod.

Warmer water in the Gulf also has knocked down populations of other marine life, including some we eat (or once ate) such as northern shrimp and cod.

For hundreds of years, cod in the northwest Atlantic was one of the world’s richest fisheries. Back in the 1970s, my older brother took a trip to Georges Bank as a whale watcher on a giant Russian factory ship. At night, the sea looked like a city, dotted with the lights of dozens of fishing vessels busily sucking up cod and everything else on the seafloor.

Cod never recovered. The U.S. soon took control of our waters out 200 miles and managed the seafood take as well as it could. But most of the cod we eat now comes from China or Iceland.

Today climate change is delivering not just disruptions in ocean temperature and circulation patterns but acidification, extreme storms, loss of mangroves and marshes… As fisheries are disrupted around the world, the familiar difficulties of managing them get worse.

We don’t really know how to model newly emerging marine ecosystems, Tatiana Rynearson of the University of Rhode Island remarked at the Metcalf session. We lack the years of data needed to understand the fluctuations in conditions and populations, as Jorge García Molinos and colleagues pointed out in a 2015 paper.

Our need for long-term ocean monitoring and related research couldn’t be clearer, but climate change research is under heavy attack in the U.S.

Fortunately, compared to most of the waters of the world, we do have good historical information on Gulf of Maine waters and seafood. And while lobsters are a luxury food, they offer a positive example for management.

Unlike the case in some other states, Maine fishers must toss back lobsters that are too big as well as too small. Simulations have shown that saving the big ones has helped the shellfish survive the fishing onslaught in the Gulf, where 90% of legal-size lobsters are caught each year, Pershing said.

The saga of Maine lobsters, of course, rolls on. The catch dropped significantly in the last two years, and the highest landings keep moving north.

Watching the river flow

The Thames Barrier is still prepped for decades defending London against high water.

On Tuesday, the warmest winter day ever recorded in Britain, there was not a cloud in the sky over the Thames Barrier. A tug calmly pulled its barge through one of the channels in the Barrier, which shuts off the Thames when the incoming tide will rise over sixteen feet. This offbeat superdam doesn’t look like anything else: a necklace of giant steampunk silver mussel shells stretched a third of a mile across the river. London began seriously contemplating means of protection after a major dousing in the great North Sea storm of 1953. The Barrier went into operation three decades later. It has decades of usefulness ahead; although climate change was not considered in its design, sea levels along the southern English coast aren’t inching up from geologic causes as fast as originally expected. The Barrier has been shut about 200 times, 50 of them in the 2013/2014 season, when the culprit was not super surges from the ocean but super rain surges that incoming tides would have pumped up further. “It is designed to be bomb-proof and failure-proof,” the Londonist once noted. “When a 3,000-tonne dredger hit the Barrier in 1997, the ship sank. The Barrier lost a ladder.” One of these decades, the enormous wall may be supplemented by a much more enormous dike downstream. In the meantime, “the structure is fundamental to the lives of millions of Londoners,” the London Review of Books commented, “which may be the reason very few of them want to look at it.”

Canaries in a coal-mined world

Environmental writers tell great stories about life across our fast-changing globe.

We’re seeing a remarkable series of stories about climate change and other manmade or partly manmade threats—some even complete with hints of solutions. Here’s a fairly random baker’s dozen from this striking crop (hmm, only two of these pieces come from for-profit publications).

Crossing the Ts in diabetes

Advances in cancer immunotherapy may help autoimmune therapies defend themselves.

allogeneic label

Is human immunology basically too crazy complex for the human mind? Evidence to date suggests yes, at least for my mind.

In almost every story I write about cancer immunology or autoimmune disease, I learn about previously unknown (to me) functions within the three-ring circus of immune cells. Or I find out about yet more types of these cells, like double-negative T cells, which can defend against graft disease and maybe type 1 diabetes. Who knew?

Well, yeah, thousands of immunologists.

All of us who follow cancer research, though, do know a (simplified) version of one genuine breakthrough in immunology, checkpoint blockade inhibitors, which garnered Nobel Prizes last October.

These drugs take on one of deepest questions in cancer biology: why the immune system doesn’t snuff out cancer cells, which by definition are genetically abnormal, often wildly abnormal.

Checkpoint blockades can hold off the T cells on patrol for just such outsiders. It turns out that a protein on the surface of tumor cells called PD-L1 can grab onto a surface protein on the T cell called PD-1 and so disarm the T cell. (Nothing to look at here, officer! Ignore my multiple heads and antitank guns!)

Other headlines in cancer immunotherapy come from chimeric antigen receptor T (CAR-T) cell drugs, treating patients with certain blood cancers in which B cells go bad. The two such drugs with FDA approval work by taking T cells from the patients, reengineering the T cells to attack those cancerous B cells, and reinserting the T cells.

This method is often effective when nothing else works, but is always worryingly slow and extremely costly.

So there’s plenty of work in labs, and a few clinics, to take a logical but intimidating next step: Engineering off-the shelf T cells to do the job, hiding them from each patient’s immune system with tricks learned from checkpoint blockade research and similar  immunology findings.

Still with me?

Okay, if those cell-shielding techniques eventually work, can a similar attack be made in autoimmune diseases such as type 1 diabetes?

In type 1 diabetes, effective ways to stop the autoimmune attacks from trigger-happy T cells exist only in lab mice. And that’s a problem not just in slowing or stopping disease progression but in trying to treat it. The most promising current approach is to encapsulate insulin-producing beta cells. This has been pursued for many decades, with many barriers. Perhaps the highest (if least surprising) barrier is that the capsules always get clogged up.

The latest capsule approaches, starting with beta cells made by reprogramming cells, try sophisticated material-science strategies to blunt this attack and may do much better.

But as long as we’re already playing genetic games with those engineered beta cells, why not also try  immune-evading tricks similar to those being studied in CAR-T experiments?

That’s the basic idea behind efforts by Altheascience, a Viacyte/CRISPR Therapeutics collaboration, and others. Which just maybe will produce capsules that, replaced every year or so as necessary, are working cures for type 1 diabetes. Which we would all fully understand.

High water marks

What does the Venice Architecture Biennale say about resilience to climate change? Not so much yet.

 

Now is the start of acqua alta season in Venice, when high tides occasionally flood low-lying areas like Saint Mark’s Square and sometimes sweep across neighborhoods around the city.* As we jumped on a vaporetto waterbus one warm sunny day, platforms of temporary pedestrian walkways were stacked nearby.

We were off to the Venice Architecture Biennale, the remarkable collection of exhibits from many countries. I was particularly curious about how the huge show would reflect the call for resilience to rising sea levels, scarier storms, droughts, heat waves and the other deadly baggage now arriving courtesy climate change.

Venice has been sinking into its lagoon by about a millimeter a year for hundreds of years. Three decades ago Italy launched the MOSE megaproject, building gates to close three entries to the lagoon against high tides. When and how well the gates will operate still seems uncertain. Perhaps it was unsurprising that Venice’s own pavilion said little about climate change, although it did emphasize advances in predicting tides.

Among the national pavilions, mentions of climate change were rare. This didn’t reflect any lack of brilliant conceptions and designs. Strikingly, many of the most intriguing pavilions didn’t focus on new construction. The French exhibit presents 10 abandoned buildings adopted for cultural use or aiding the homeless, for example. The Egyptian pavilion dives into how street vendors capitalize on public spaces in Cairo.  Other exhibits, such as the Argentinian, do highlight natural landscapes and what’s left of them.

You could profitably spend hours in many of these intriguing spaces. I didn’t, and I probably missed a lot of serious thinking about climate resilience. I definitely although accidentally skipped the Antigua and Barbuda pavilion, which was not at the main Biennale sites but in a monastery near the center of Venice. Last year, Hurricane Irma hit Barbuda with winds over 150 miles per hour and destroyed most of the island’s buildings. All 1,800 residents were evacuated. Unsurprisingly, the pavilion’s theme centers on climate change: Environmental Justice as a Civil Right.

Giant dikes and other grand engineering projects will help us deal with climate change, but most of the heavy lifting will come from rethinking local architecture and design. The Biennale was awash in young architects from around the world, our hope for resilience.

*  Two days after I wrote this, Venice was hit by a storm bringing the worst acqua alta event in years, flooding most of the city.

In good weather, Venice is all about eye candy, not just in architecture and art.