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.

Beta living through stem cells

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

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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.”

The write stuffing

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When I graduated from high school, all I really knew professionally was that I wanted to write on many topics. Last weekend when people at my high school reunion asked politely what I wrote about, I did find myself saying, many topics—in fact, way more now than when I worked as a staff journalist. Okay, I’m not covering the full human condition. Much of the universe is unexplored. But so far this year I’ve done stories about medical hackathons and crowdsourced scientific challenges, global data security and global financial crises (still separate topics so far!), drug development crises, the future of suburbia, steam power, gene therapyagricultural particulates, the challenges of small data in healthcare, chemical sensing on a chip, employee cross-trainingurban carbon dioxide release, jet engines, zebrafish brains, surgery by telemedicine and robotics manufacturing, among others.

Hackathon crowd control

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Crowdsourced challenges are now an established part of the medical research ecosystem, especially for data analysis problems such as finding the best genomic analysis techniques or new ways to interpret mammography data. Writing a story about these competitions for Nature, I’ve been struck by the rapid spread of their most intense form: the medical hackathon.

Described today in a Science Translational Medicine review, these hackathons (or “datathons”) take place over a weekend or a few evenings, bringing together some mix of medical scientists and engineers, data scientists, clinicians, patients, medical entrepreneurs, public health advocates and other interested parties. Participants “are encouraged to collaborate, fail fast and iterate.”

Hundreds of medical hackathons have been held. Some encourage multiple groups to study the same clinical problem with the same data and compare conclusions. Other hackathons are all about idea generation. The events may target specific threats such as the Zika epidemic, or more general topics such as improved intensive care, or a free-for-all of unsolved medical problems.

Like software hackathons, the medical hackathon “integrates collaboration, idea generation, and group learning by joining various stakeholders in a mutually supportive setting for a limited period of time,” the STM authors say.

Key is the face-to-face mashup of expertise and views, which doesn’t come easily on the outside. “It is difficult to establish a platform for the realtime, respectful, and effective exchange of ideas among specialists who are usually separated by time, space, methods, attitudes, and terminology,” they point out.

This difficulty holds even for global crises like Zika. But hackathons around the world are addressing the rapidly spreading virus, among them one held at Massachusetts General Hospital earlier this month. Among the resulting proposals:

  • An app for crowdsourced mosquito surveillance data collection, with games
  • Larvicide automatic dispensers
  • A public health online rumor-squashing campaign
  • Hairnet-like nets to cover open water containers
  • Applying new diagnostic technology to detect the virus in pregnant women
  • A mosquito larva finder, with a microscope add-on to a smart phone that samples standing water, analyzes for type of larva and adds GPS location data.

As often with more established crowdsourcing competitions like the Dream Challenges, we don’t know which if any of these early results will be driven all the way into the clinic. But the promise is real.