Ark de Triage

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

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“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.

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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

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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.

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An Engine for solving societal problems

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

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“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.