Pub read

It’s a golden age for magazines on science and the environment.

 

Each year as I help to filter out the National Association of Science Writers’ Science in Society Awards nominees, I run across remarkable new-to-me publications.  You could spend wholly unworkable amounts of time on their dazzling stories and videos.

Some of these magazines seem to generate cash (Quartz offers one clue: sponsored content that you actually might want to read.) But most of the pubs run on institutional funding and/or donations, which is not always a recipe for long-term survival. Here are a few favorites, each with a story or two picked fairly randomly (except that I wrote two of them).

Aeon, Votes for the future
Ensia, Could this one simple idea be the key to solving farmer–environmentalist conflicts? and With storms intensifying and oceans on the rise, Boston weighs strategies for staying dry
Hakai, Damming Eden
High Country News, Why western wildfires are getting more expensive
Mongabay, Abandoned by their sponsors, Madagascar’s orphaned parks struggle on
Pacific Standard, Libya’s slave trade didn’t appear out of thin air
Quanta, Artificial intelligence learns to learn entirely on its own
Quartz, AI is now so complex its creators can’t trust why it makes decisions
Sapiens, Sea level rise threatens archaeological sites
Undark, The allure and perils of hydropower and Putting digital health monitoring tools to the test

Towers of power

Wind turbines go to work 16 miles off the Rhode Island coast.

Offshore wind turbines seemed a bit, well, gimmicky to me until a few years ago when I saw a farm calmly spinning its blades as I flew home from Europe. Anything that keeps working in the North Sea is entirely real. Now they have arrived in 600-foot-form off the New England coast, as I saw last month in a trip to Deepwater Wind’s installation off Block Island (thanks, Noelle Swan and the New England Association of Science Writers!). These giant beasts won’t always be easy to maintain, as we saw watching a crew struggling to jump onto one tower from a support vessel in gentle six-foot swells from Hurricane Maria. The 240-foot blades are no favor to offshore birds. But Deepwater Wind seems to have made every reasonable effort to minimize and monitor the overall environmental impact of the turbines, as attested by the National Wildlife Federation scientist onboard our fast ferry. Ocean wind turbine technology is advancing rapidly, one example being the replacement of the traditional gearbox with a GE direct-drive permanent magnet generator, noted Willett Kempton of the University of Delaware’s ocean wind power program. Wind turbines can tap steady winds at sea, where they can be built much larger than on land, and a wealth of projects are planned along the U.S. east coast. Yes, they’re designed to survive hurricanes, although maybe not a problem like Maria. And although offshore wind still can’t produce power here as cheaply as fossil-fuel plants, European wind costs are already below that mark.

Public Spectacle

A beacon of hope in a changing climate.

kid Spectacle

On a clear hot August day you can take a ferry to Spectacle Island and walk a winding path up to its northern summit, admiring wildflowers and eating blackberries. The summit is the highest point of land on Boston Harbor, with low wooded islands scattered around.

Off to the east you can spot a windmill near the huge sludge-digesting eggs of Deer Island, and a second windmill a few miles south at the tip of the Hull peninsula. These two points of land bracket the entrance from Massachusetts Bay to the harbor’s inner archipelago.

One distant day, Deer Island and Hull also may anchor a massive sea barrier, holding off an ocean that’s now projected to climb as much as eight feet by 2100.

Today it’s hard to imagine how we might start to build such a Big Dike, given our current politics.

But you can also see hopeful signs on this Spectacle for our ability to clean up our own messes.

The first time I sailed past the island it was a garbage dump, with the remnants of a horse-rendering plant buried under many feet of still-smoldering refuse.

Now that’s all taken away and replaced by fill from the Big Dig. The island was reengineered and replanted. Rich ecosystems began to reappear. On summer days like this, children swim a stone’s throw away from the site of the old factories.

In wildness is the preservation of the world, as Thoreau said. But not just in wildness.

Blossoms in biomedicine

The remarkable global push for cancer immunotherapies.
El_Talayón.byJose Ignacio Martinez Navarro
Editing a Nature special report on cancer immunotherapies, I’m struck most by the sheer scale of the development effort. Something like 3,000 clinical trials are underway, 800 of them combining treatments. The FDA has approved five checkpoint inhibitors, designed to unleash T cells against tumors. The agency seems close to approving the first CAR-T cell treatment, in which a patient’s T cells are removed, reengineered to attack cancer cells, regrown in volume and returned to the patient. Old dogs of immunotherapies are learning new tricks. Some newer approaches are getting much attention—notably personalized neoantigen vaccines, in which individual tumors are sequenced to give clues on how to best target their unique sets of immune-system-alarming antigens. Some clinical trials fail, some do surprisingly well.  The competition is more than intense and trials are not always carefully planned or analyzed. But the landscape is changing.

Ark de Triage

What should we prioritize to try to save from the flood tide of extinction?

Big_Ark_in_Dordrecht_3

“The world is on fire, and we have to do something about it,” said Kate Jones, an ecologist with University of College in London.

Jones was one of the speakers at two Harvard panels last month about the species extinction perils of our Anthropocene age: climate change, overfishing and overhunting, pollution, loss of habitat, invasive species, sea level rise, ocean acidification and all the ugly rest.

Extinction threats are not like a field of bullets hitting everything equally, noted Jones, speaking at a session on Human Imprints on the Tree of Life. Primates are at greater risk than most mammals. Amphibians, palms and corals are particularly vulnerable. Ditto species on islands. Animals with large body sizes, long lives and small ranges are vanishing. Along with, of course, so many other forms of life.

Facing this global storm of extinction with severely limited resources, what should conservation groups and governments prioritize?

One framework for decisions is to safeguard plants and animals with particular values to humans, as food, fuel, eye candy or just insurance for the future, the scientists said. Another framework is to consider the tree of life—protecting genetic diversity so that we can better understand biology and maybe exploit that understanding down the road. (Saving, for instance, the ginkgo tree, full of idiosyncrasies after branching off from other trees 100 million years ago.)

Habitat protection initiatives don’t always follow these outlines, naturally enough. As one audience member noted, many projects in Britain aim to preserve butterflies that remain happily common elsewhere in Europe.

“Most conservation is local, which is fine,” said Ana Rodrigues of the French National Center for Scientific Research. But very few resources work at a global level, Rodrigues emphasized.

One of the few is the Evolutionarily Distinct & Globally Endangered (EDGE) program led by the Zoological Society of London. “We can take attention away from charismatic megafauna like pandas, which are cute and fluffy with big eyes,” remarked Jones. Instead, attention can be paid to offbeat creatures like the pink fairy armadillo. (“It’s another poster child but I think it’s spreading out the love.”)

“We’re in deep trouble,” said Yale botanist Michael Donoghue. “We have to act quickly. The problem is, there are too many things we value.”

Many forms of ecological damage have spread surprisingly quickly across vast areas of ocean, noted biologists at an Ocean Evolution Today seminar. Jellyfish are on the march  as we vacuum up commercial finfish. Two-thirds of the Great Barrier Reef’s coral died off in two years. “In the Arctic, ice algae is disappearing and the entire food web is compromised,” commented Samantha Joye of the University of Georgia.

All too often this marine damage is invisible to most of us, said Boston University’s Randi Dawn Rotjan. Even survival stories can be worrisome–for instance, the killifish that have evolved to shrug off PCB-laced harbors.

More generally, “I’m worried that my children will jump into the water and not know what they haven’t seen,” Rotjan said.

“The most important ecosystems on the planet are almost unknown,” pointed out Bruce Robison of the Monterey Bay Aquarium Research Institute. One case in point: the ocean animals that migrate in “uncountable numbers” up toward the surface at night and then back down during the day, which brings carbon out of the surface waters.

Or we can think of the seafloor hot water vents discovered 40 years ago, which stream out key nutrients and may act “like the ocean’s multi-vitamins,” said Harvard’s Peter Girguis. Life throughout the sea, he added, “is linked to things that happen in the deepest darkest parts of the ocean.”

The scientists applauded the spread of marine sanctuaries, which can provide significant safeguards if established (and enforced) on sufficient scale. So far, sanctuaries have grown most notably in sparsely populated stretches of the Pacific. (The Republic of Kiribati’s Phoenix Islands Protected Area is a coral archipelago the size of California with exactly 24 people, living on one island, Rotjan said.) The High Seas Alliance aims to extend this strategy with protected areas in the no-man’s-lands of the open ocean.

Another positive sign is the rapid growth of sustainable aquaculture, to supplement and replace capture fisheries.

And we also can see payoffs of local and regional marine renewal efforts, such as the massive cleanup of Boston Harbor. Last month, out with a boatful of biologists for a conference hosted by Northeastern University, we were cheered to see harbor porpoises calmly working the clean waters of the Mystic River, in what not long ago was the dirtiest harbor in the U.S.

Top, the “life-size” version of Noah’s Ark built by Johan Huibers of the Netherlands. Bottom, clockwise from panda: Ice algae, pink fairy armadillo, ginkgo berries, mussel.

Moving the needles

Updates on progress in research against type 1 diabetes.

BetaBionics

JDRF New England’s annual research briefing offers a quick summary of research for type 1 diabetes. Here are four snapshots from last night’s talks by JDRF’s Julia Greenstein and University of Colorado’s Peter Gottlieb:

  1. The march continues toward an “artificial pancreas” that automatically provides just the right amounts of insulin around the clock. The first of four NIH-sponsored pivotal clinical trials kicked off in February. Many of us are most intrigued by the Beta Bionics combo device, designed to deliver both insulin (which lowers blood glucose levels) and glucagon (which raises them). This device is a few years behind some of its competitors, but we like it for the same reason we would prefer a self-driving car with brakes.
  1. JDRF has awarded more than 50 grants for research on encapsulating insulin-producing beta cells derived from stem cells, to initiatives such as the Boston Autologous Islet Replacement Therapy Program. News from the much-watched Viacyte clinical trial, however, is not so good. The Viacyte capsule prevents against some immune response but generates a foreign-body reaction. Next–generation encapsulation technologies may do better on immune response but must still grapple with another fiendishly tricky issue—admitting suitably high levels of oxygen to the beta cells. (The pancreas is even hungrier for oxygen than the brain, Greenstein noted.)
  1. For decades, immunologists in both cancer and autoimmune diseases like type 1 diabetes made important discoveries that didn’t translate into better treatments. That unhappy situation has changed bigtime with cancer immunology, and diabetes researchers are now adopting two general strategies in cancer treatment. One strategy is to recognize that the disease may work quite differently in different people—for example, in trials of drugs designed to delay or prevent progression of the disease, often one group responds much better than another. So “personalized medicine”, tailored to specific groups of patients, may recast the field in type 1 just as it has done with many forms of cancer. The second strategy aims to confront the complexity of the disease by combining treatments, as the University of Miami’s Jay Skyler has proposed.
  1. No clear winners have ever emerged from the dozens of trials of drugs designed to delay or prevent type 1 diabetes onset. One contender that’s still standing is oral insulin acting as a vaccine. Drug companies have chased the elusive goal of an insulin pill for a century (with a few recent signs of progress) but such pills typically get ripped apart in your gut without lowering your blood glucose levels. However, the resulting fragments of insulin may generate an anti-immune protective response in the pancreas. Early clinical tests of this vaccine concept (such as this one reported in 2015) have shown promise for some patients. The latest clinical results, including early findings from a phase II trial with higher doses, will be announced on June 12th at the American Diabetes Association annual scientific sessions. We’ll be watching!

10 farm fish stories

What aquaculture experts tell me about the world’s fastest-growing food source.26326495102_757a4e2476_k

  1. Nigerian catfish are bred so densely you can walk across their ponds.
  2. “In an urban environment, why not use a rooftop to grow fish in a couple of recirculating ponds?”
  3. China grows grass carp in quantities equal to the catch of the entire U.S. fishing fleet.
  4. “Everyone’s working hard to reduce the use of fishmeal and fish oil in feed, and to fool the fish into thinking they are eating what they want.”
  5. All the tilapia we eat are male, with females forced that way early in life.
  6. “Many agricultural landscapes are becoming more saline and facing more seasonal inundation from the sea. There’s a big opportunity for aquaculture explicitly to be part of a planned transition that can not only recover but actually dramatically increase the value of these landscapes.”
  7. Shrimp lack an immune system.
  8. “In Africa, the sooner we move past small-scale aquaculture, the better. It’s a dead duck.”
  9. Eight miles off Panama’s Atlantic coast, cobia destined for plates in the United States fatten up in high-tech cages.
  10. The world needs to grow 30 million more tons of fish each year by 2050: “We mostly know how, but is there a will to do it?”

Photos courtesy WorldFish.

Working out

Okay, what really happens down the road to all our jobs?welcomeWe know that automation replaces many human jobs and generates many others, and that artificial intelligence will accelerate this creative destruction. Historically, the default view among business and technology leaders, supported mostly by hand-waving, is that this unstoppable march will bring a wealth of new jobs, if only the masses somehow can receive proper technological education.

It’s hard to assess the recent historical record on job loss versus gain, although today’s New York Times offers an interesting take. And while we can easily spot job losses, new jobs created by machines, “almost by definition, are harder to imagine,” as MIT economist Erik Brynjolfsson pointed out in a session at the American Association for the Advancement of Science (AAAS) annual meeting in Boston on Saturday.

But in the past couple of years the public discussion has grown more worried, with one dark perspective on implications well described in a poorly titled essay by Rutgers historian James Livingston.

At the AAAS session, Harvard computer scientist David Parkes presented some relevant thoughts from the 100 Year Study on Artificial Intelligence project. Here are a few quotes from the study’s report on AI and real life in 2030, published last September:

  • “AI will gradually invade almost all employment sectors, requiring a shift away from human labor that computers are able to take over.”
  • “To date, digital technologies have been affecting workers more in the skilled middle, such as travel agents, rather than the very lowest-skilled or highest skilled work. On the other hand, the spectrum of tasks that digital systems can do is evolving as AI systems improve, which is likely to gradually increase the scope of what is considered routine. AI is also creeping into high end of the spectrum, including professional services not historically performed by machines.”
  • “A spectrum of effects will emerge, ranging from small amounts of replacement or augmentation to complete replacement. For example, although most of a lawyer’s job is not yet automated, AI applied to legal information extraction and topic modeling has automated parts of first-year lawyers’ jobs. In the not too distant future, a diverse array of job-holders, from radiologists to truck drivers to gardeners, may be affected.”
  • “As labor becomes a less important factor in production as compared to owning intellectual capital, a majority of citizens may find the value of their labor insufficient to pay for a socially acceptable standard of living. These changes will require a political, rather than a purely economic, response concerning what kind of social safety nets should be in place to protect people from large, structural shifts in the economy. Absent mitigating policies, the beneficiaries of these shifts may be a small group at the upper stratum of the society.”
  • “Longer term, the current social safety net may need to evolve into better social services for everyone, such as healthcare and education, or a guaranteed basic income. Indeed, countries such as Switzerland and Finland have actively considered such measures. AI may be thought of as a radically different mechanism of wealth creation in which everyone should be entitled to a portion of the world’s AI-produced treasure.”

At another packed AAAS session, Alta Charo, professor of law and bioethics at the University of Wisconsin at Madison, gave a masterful quick summary of the history and findings of the report on human genome editing from the National Academy of Science. Released last week, this report’s recommendations drew plenty of public attention—far more than last fall’s AI in 2030 report, although AI will have much greater impact in the next decade or two or three.

Clean genes

Twenty years on, James Wilson’s vision is redeemed.

aav_3-02017 probably will be the year in which gene therapies will be first approved by the Food and Drug Administration—a positive move in a year that’s not looking so positive overall.

These successes were built in part on experience from a tragic clinical failure back in 1999, with the death of a teenage volunteer in the far-too-aggressive early gene therapy trial spearheaded by James Wilson of the University of Pennsylvania.

“This event had far-reaching effects on the trajectory of gene therapy research and oversight of all clinical trials,” Wilson noted a decade later in a commentary on lessons learned.

“My deepest regret is that a courageous young man who agreed to participate in this clinical trial with the hope of making life better for others with this disease lost his life in the process,” he wrote. “The immunologic response that precipitated the lethal syndrome of systemic inflammation was unanticipated and not predicted based on the preclinical and clinical data available at the time. However, some of the problems in the design and conduct of the clinical trial that surfaced in the subsequent investigations were real and absolutely unacceptable and ultimately were my responsibility.”

Wilson lost his government research funding. But with initial backing from a former mentor at GlaxoSmithKline, he went back into the lab to develop more advanced gene therapy delivery systems,  “adeno-associated” virus (AAV) vectors, that are a cornerstone of many therapies now approaching approval.

“We characterized these vectors and started to distribute them to academic researchers,” Wilson told me last year for a story in Nature. “Over the next 10 to 15 years, these vectors have formed the basis for most of the clinical translation and most of the companies that have been founded.”

One of these companies is Spark Therapeutics, whose treatment for a rare genetic eye disease may be the first gene therapy to get FDA approval. Spark also is among several biotechs with candidates for treating hemophilia that appear both surprisingly effective and, so far, acceptably safe.

True, no one really knows if the effects of these new therapies will last a lifetime. Or exactly how payers will view their high prices.

“If we can deliver transformative therapies, we’ll see huge effects on the practice of medicine,” said Wilson, who is now leading the creation of a third generation of AAV vectors (above). “The concept is so fundamental: engineering a cell to modify expression of a gene to prevent, cure or treat a disease. This will only grow.”

Museums and the shock of the old

Coming face to face with the Dama de Elche

 OLYMPUS DIGITAL CAMERA

Millennia later, physical reality still has its moments, at least in museums.

In Madrid last week for Thanksgiving, at the quite wonderful National Archeology Museum, I suddenly realized that I was looking at the Dama de Elche. I hadn’t known that this limestone bust from the 4th or 5th century BC was life-size. Or so haunting, so human. She stands near two full-length compatriots, the irritable Dama de Biza and the huge-eyed Dama del Cerro de los Santos. No one is smiling. Who were these women? Were there ever Señores de Elche, Biza or Cerro de los Santos?

The museum’s remarkable collection of artifacts also includes the beautiful sandals below, which look almost as wearable as when their Neolithic weaver tied the last knots 7,000 years ago. Museums clean up these ultra-rare survivors but leave almost all of their mysteries, along with the realization that they were created by people very much like us.

sandals_neolithic

An Engine for solving societal problems

MIT’s accelerator brings an incubator and funding to startups that matter.

the_engine_logo

“One of my frustrations as an academic is that over the last twelve years we’ve produced a lot of really useful methods and techniques, and almost none of them has been put into practice,” one prominent MIT professor told me earlier this year. “This is not an unusual problem for academics. But it’s frustrating to have things that you know could help and they’re not helping.”

Generating the intellectual property (IP) is only the very first step on the road to the real world. Established companies often are not very interested in IP, even game-changing IP. They are more likely to want prototypes, and people who know how to build the prototypes.

They want, in brief, to work with startups.

That’s one reason why this professor launched a startup. It’s also one reason why MIT actively spreads the entrepreneurial gospel to students and staff who might not have considered it a few years back, and keeps deepening its “environmental ecosystem” of competitions and advisory networks and resources like the Startup Exchange.

And it’s the thinking behind the Engine, the startup accelerator that MIT president L. Rafael Reif announced yesterday. The Engine will combine an incubator with funding for startups focused on real needs.

“When it comes to the most important problems humanity needs to solve — climate change, clean energy, fresh water and food for the world, cancer, and infectious disease, to name a few — there is no app for that,” as Reif explained in the Boston Globe. “We believe the Engine will help deliver important answers for addressing such intractable problems — answers that might otherwise never leave the lab.”

Venture capitalists do a reasonable job of funding many tech companies, but very few VCs are interested in startups that may take more than five years to pay off. The Engine won’t sponsor quick-turnaround firms, or companies that join the thundering herds of marketing middlemen, or oddities like the outfit that claims to deliver wine matched to your DNA.

Instead the funds might go to biotechs, like Oxalys, which do very well if they can even get their drug candidates into first clinical trials within a few years. Or makers of industrial products, like Dropwise’s energy-saving coatings for power plants, which manufacturers probably will adopt quite slowly because that’s how that industry works. Or any number of truly innovative, truly needed products and services.

It will take a decade or more to see how the Engine’s bets turn out. Many will fail. But these are bets we need.

Beta living through stem cells

Insulin-producing cells will be tested first in patients lacking a pancreas.

insulin

Diabetes is way complex. “But it’s a simple disease conceptually—your body doesn’t produce enough insulin,” notes Joslin Diabetes Center researcher Gordon Weir.

In type 1 diabetes, an autoimmune attack wipes out insulin-producing beta cells, which are found in clusters of pancreatic cells called islets. In type 2 diabetes, the beta cells are still there but not hauling all the freight. That disease can be treated with many other types of drugs, along with lifestyle changes. But over time, beta cells wear out. In fact, more people with type 2 take insulin than people with type 1.

And there’s no way to make insulin injections pleasant or easily controllable or as good as insulin production by beta cells.

Thus the huge interest in a long-term research project spearheaded by Harvard’s Doug Melton to create working beta cells by manipulating stem cells. An update on the ambitious project from Melton, Weir and other partners drew a crowd at Harvard on Monday.

Making insulin-producing cells good enough for clinical trials “turns out to be rather difficult; it took more than a decade,” Melton said. “We haven’t made it really perfect, but it’s at the goal line.”

Technology from Melton’s lab has been licensed exclusively to the startup Semma Therapeutics, which is joining with Joslin, Brigham & Women’s Hospital and Dana-Farber Cancer Institute to move toward clinical trials. Traveling under the ungainly title of the Boston Autologous Islet Replacement Therapy Program (BAIRT), the collaboration launched in June.

The first BAIRT studies, starting at least three years from now, will not be among people with type 1 diabetes. Instead, they will recruit people who have had their pancreases removed, usually because of uncontrollable pain after the organs are chronically inflamed by years of heavy drinking.

This approach bypasses the biggest problem in cell treatments for type 1 diabetes: the body renews its autoimmune attack and wipes out the newly introduced cells. “We decided to solve one problem at a time,” Melton explained.

Patients who have prostatectomies often now are given islet cells salvaged from their own pancreas, which helps to improve their diabetes control, but those cells may themselves be damaged or in short supply, said Brigham surgeon Sayeed Malek. Transplants of brand-new beta cells, made from the patients’ own blood, should help.

These reengineered cells will be injected in the arm, where they will be easy to monitor  and to remove if necessary, said Semma CEO Robert Millman. Decades of experience transplanting cells from cadavers has shown that “you can put beta cells just about anywhere,” Weir added.

Against autoimmunity. If all goes well, the project will continue into trials for type 1 diabetes with non-personalized beta cells, where the autoimmune attack will be blunted via encapsulating the cells. Seema is spending about half its budget on encapsulation technologies, Millman said.

Encapsulation is the near-term solution to fend off the autoimmune attack. “The long-term solution is to use the power of biology to understand why the immune system has made this mistake,” Melton remarked.

He briefly mentioned two promising research thrusts. One effort is to learn from the rapid advances in knowledge about how cancer cells dodge the immune system.

Another, led by Chad Cowan of Massachusetts General Hospital, aims to create a “universal donor pluripotent stem cell.” Missing all the billboard signs that alert immune enforcers, these cells could play a role like that of O-positive cells in blood transfusions.

Asked about his own take on the causes of type 1, Melton mentioned one theory that the autoimmune attack may be triggered by gut cells that naturally produce insulin or similar substances under certain conditions.

Slow and steady. Bringing beta cell therapies to the clinic will be a marathon march with not only many scientific steps but many regulatory steps. Millman emphasized, however, that “the FDA is working with us very early on the regulatory path.”

Among potential safety risks, all stem cell therapies must be carefully vetted to avoid the growth of teratomas—tumors with a jumbled mix of cells, usually benign. These cellular junk piles would be relatively easy to remove, but much better to avoid altogether, Millman said.

Another concern is that the cells will secrete insulin even when it’s not needed, dropping the recipient’s blood sugar levels to dangerously low levels.

There also is much cause for worry that the cells won’t last long, a major problem in transplants of cadaver beta cells. However, built-from-scratch cells function “for more than a year in mice, which bodes well for people,” Weir commented. And Millman pointed out that the cells resemble juvenile cells, which may help them withstand the high stresses of transplantation better than worn-out adult beta cells do. “We hope these almost pristine cells going into the patients will last a lot longer,” he said.

None of this will come cheap. Asked about pricing for cell therapies, way down the road when and if they hit the market, Millman was understandably wary. Initial costs for these treatments will be very high, accompanied by very close regulatory scrutiny. Semma has raised about $50 million, but “we need philanthropy and we need institutions to support this,” he said.

Melton suggested, though, that successful cell-based therapies will make complete  economic sense, given the soaring numbers of people with diabetes and the huge costs of diabetes care. Each year the world spends about $30 billion on insulin alone. “Diabetes is not an orphan disease,” he said. “The cost will come down very quickly.”