Cancer ‘vaccine’ eliminates tumors in mice

February 05, 2018

Injecting minute amounts of two immune-stimulating agents directly into solid tumors in mice can eliminate all traces of cancer in the animals, including distant, untreated metastases, according to a study by researchers at the Stanford University School of Medicine.

The approach works for many different types of cancers, including those that arisespontaneously, the study found.

The researchers believe the local application of very small amounts of the agents could serve as a rapid and relatively inexpensive cancer therapy that is unlikely to cause the adverse side effects often seen with bodywide immune stimulation.

“When we use these two agents together, we see the elimination of tumors all over the body,” said Ronald Levy, MD, professor of oncology. “This approach bypasses the need to identify tumor-specific immune targets and doesn’t require wholesale activation of the immune system or customization of a patient’s immune cells.”

One agent is currently already approved for use in humans; the other has been tested for human use in several unrelated clinical trials. A clinical trial was launched in January to test the effect of the treatment in patients with lymphoma.

Levy, who holds the Robert K. and Helen K. Summy Professorship in the School of Medicine, is the senior author of the study, which was published Jan. 31 in Science Translational Medicine. Instructor of medicine Idit Sagiv-Barfi, PhD, is the lead author.

‘Amazing, bodywide effects’

Levy is a pioneer in the field of cancer immunotherapy, in which researchers try to harness the immune system to combat cancer. Research in his laboratory led to the development of rituximab, one of the first monoclonal antibodies approved for use as an anticancer treatment in humans.

Some immunotherapy approaches rely on stimulating the immune system throughout the body. Others target naturally occurring checkpoints that limit the anti-cancer activity of immune cells. Still others, like the CAR T-cell therapy recently approved to treat some types of leukemia and lymphomas, require a patient’s immune cells to be removed from the body and genetically engineered to attack the tumor cells. Many of these approaches have been successful, but they each have downsides — from difficult-to-handle side effects to high-cost and lengthy preparation or treatment times.

“All of these immunotherapy advances are changing medical practice,” Levy said. “Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumor itself. In the mice, we saw amazing, bodywide effects, including the elimination of tumors all over the animal.”

Cancers often exist in a strange kind of limbo with regard to the immune system. Immune cells like T cells recognize the abnormal proteins often present on cancer cells and infiltrate to attack the tumor. However, as the tumor grows, it often devises ways to suppress the activity of the T cells.

Levy’s method works to reactivate the cancer-specific T cells by injecting microgram amounts of two agents directly into the tumor site. (A microgram is one-millionth of a gram). One, a short stretch of DNA called a CpG oligonucleotide, works with other nearby immune cells to amplify the expression of an activating receptor called OX40 on the surface of the T cells. The other, an antibody that binds to OX40, activates the T cells to lead the charge against the cancer cells. Because the two agents are injected directly into the tumor, only T cells that have infiltrated it are activated. In effect, these T cells are “prescreened” by the body to recognize only cancer-specific proteins.

Cancer-destroying rangers

Some of these tumor-specific, activated T cells then leave the original tumor to find and destroy other identical tumors throughout the body.

The approach worked startlingly well in laboratory mice with transplanted mouse lymphoma tumors in two sites on their bodies. Injecting one tumor site with the two agents caused the regression not just of the treated tumor, but also of the second, untreated tumor. In this way, 87 of 90 mice were cured of the cancer. Although the cancer recurred in three of the mice, the tumors again regressed after a second treatment. The researchers saw similar results in mice bearing breast, colon and melanoma tumors.

Mice genetically engineered to spontaneously develop breast cancers in all 10 of their mammary pads also responded to the treatment. Treating the first tumor that arose often prevented the occurrence of future tumors and significantly increased the animals’ life span, the researchers found.

Finally, Sagiv-Barfi explored the specificity of the T cells by transplanting two types of tumors into the mice. She transplanted the same lymphoma cancer cells in two locations, and she transplanted a colon cancer cell line in a third location. Treatment of one of the lymphoma sites caused the regression of both lymphoma tumors but did not affect the growth of the colon cancer cells.

“This is a very targeted approach,” Levy said. “Only the tumor that shares the protein targets displayed by the treated site is affected. We’re attacking specific targets without having to identify exactly what proteins the T cells are recognizing.”

The current clinical trial is expected to recruit about 15 patients with low-grade lymphoma. If successful, Levy believes the treatment could be useful for many tumor types. He envisions a future in which clinicians inject the two agents into solid tumors in humans prior to surgical removal of the cancer as a way to prevent recurrence due to unidentified metastases or lingering cancer cells, or even to head off the development of future tumors that arise due to genetic mutations like BRCA1 and 2.

“I don’t think there’s a limit to the type of tumor we could potentially treat, as long as it has been infiltrated by the immune system,” Levy said.

The work is an example of Stanford Medicine’s focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.

The study’s other Stanford co-authors are senior research assistant and lab manager Debra Czerwinski; professor of medicine Shoshana Levy, PhD; postdoctoral scholar Israt Alam, PhD; graduate student Aaron Mayer; and professor of radiology Sanjiv Gambhir, MD, PhD.

Levy is a member of the Stanford Cancer Institute and Stanford Bio-X.

Gambhir is the founder and equity holder in CellSight Inc., which develops and translates multimodality strategies to image cell trafficking and transplantation.

The research was supported by the National Institutes of Health (grant CA188005), the Leukemia and Lymphoma Society, the Boaz and Varda Dotan Foundation and the Phil N. Allen Foundation.

Stanford’s Department of Medicine also supported the work.

This article was originally published by:
https://med.stanford.edu/news/all-news/2018/01/cancer-vaccine-eliminates-tumors-in-mice.html

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Nick Bostrom: What happens when our computers get smarter than we are?

February 01, 2018

Artificial intelligence is getting smarter by leaps and bounds — within this century, research suggests, a computer AI could be as “smart” as a human being. And then, says Nick Bostrom, it will overtake us: “Machine intelligence is the last invention that humanity will ever need to make.” A philosopher and technologist, Bostrom asks us to think hard about the world we’re building right now, driven by thinking machines. Will our smart machines help to preserve humanity and our values — or will they have values of their own?

What Happens If China Makes First Contact?

February 01, 2018

Last January, the Chinese Academy of Sciences invited Liu Cixin, China’s preeminent science-fiction writer, to visit its new state-of-the-art radio dish in the country’s southwest. Almost twice as wide as the dish at America’s Arecibo Observatory, in the Puerto Rican jungle, the new Chinese dish is the largest in the world, if not the universe. Though it is sensitive enough to detect spy satellites even when they’re not broadcasting, its main uses will be scientific, including an unusual one: The dish is Earth’s first flagship observatory custom-built to listen for a message from an extraterrestrial intelligence. If such a sign comes down from the heavens during the next decade, China may well hear it first.

In some ways, it’s no surprise that Liu was invited to see the dish. He has an outsize voice on cosmic affairs in China, and the government’s aerospace agency sometimes asks him to consult on science missions. Liu is the patriarch of the country’s science-fiction scene. Other Chinese writers I met attached the honorific Da, meaning “Big,” to his surname. In years past, the academy’s engineers sent Liu illustrated updates on the dish’s construction, along with notes saying how he’d inspired their work.

But in other ways Liu is a strange choice to visit the dish. He has written a great deal about the risks of first contact. He has warned that the “appearance of this Other” might be imminent, and that it might result in our extinction. “Perhaps in ten thousand years, the starry sky that humankind gazes upon will remain empty and silent,” he writes in the postscript to one of his books. “But perhaps tomorrow we’ll wake up and find an alien spaceship the size of the Moon parked in orbit.”
China’s new radio dish was custom-built to listen for an extraterrestrial message. (Liu Xu / Xinhua / Getty)
In recent years, Liu has joined the ranks of the global literati. In 2015, his novel The Three-Body Problem became the first work in translation to win the Hugo Award, science fiction’s most prestigious prize. Barack Obama told The New York Times that the book—the first in a trilogy—gave him cosmic perspective during the frenzy of his presidency. Liu told me that Obama’s staff asked him for an advance copy of the third volume.At the end of the second volume, one of the main characters lays out the trilogy’s animating philosophy. No civilization should ever announce its presence to the cosmos, he says. Any other civilization that learns of its existence will perceive it as a threat to expand—as all civilizations do, eliminating their competitors until they encounter one with superior technology and are themselves eliminated. This grim cosmic outlook is called “dark-forest theory,” because it conceives of every civilization in the universe as a hunter hiding in a moonless woodland, listening for the first rustlings of a rival.
Liu’s trilogy begins in the late 1960s, during Mao’s Cultural Revolution, when a young Chinese woman sends a message to a nearby star system. The civilization that receives it embarks on a centuries-long mission to invade Earth, but she doesn’t care; the Red Guard’s grisly excesses have convinced her that humans no longer deserve to survive. En route to our planet, the extraterrestrial civilization disrupts our particle accelerators to prevent us from making advancements in the physics of warfare, such as the one that brought the atomic bomb into being less than a century after the invention of the repeating rifle.

Science fiction is sometimes described as a literature of the future, but historical allegory is one of its dominant modes. Isaac Asimov based his Foundation series on classical Rome, and Frank Herbert’s Dune borrows plot points from the past of the Bedouin Arabs. Liu is reluctant to make connections between his books and the real world, but he did tell me that his work is influenced by the history of Earth’s civilizations, “especially the encounters between more technologically advanced civilizations and the original settlers of a place.” One such encounter occurred during the 19th century, when the “Middle Kingdom” of China, around which all of Asia had once revolved, looked out to sea and saw the ships of Europe’s seafaring empires, whose ensuing invasion triggered a loss in status for China comparable to the fall of Rome.

This past summer, I traveled to China to visit its new observatory, but first I met up with Liu in Beijing. By way of small talk, I asked him about the film adaptation of The Three-Body Problem. “People here want it to be China’s Star Wars,” he said, looking pained. The pricey shoot ended in mid-2015, but the film is still in postproduction. At one point, the entire special-effects team was replaced. “When it comes to making science-fiction movies, our system is not mature,” Liu said.

I had come to interview Liu in his capacity as China’s foremost philosopher of first contact, but I also wanted to know what to expect when I visited the new dish. After a translator relayed my question, Liu stopped smoking and smiled.“It looks like something out of science fiction,” he said.

A week later, I rode a bullet train out of Shanghai, leaving behind its purple Blade Runner glow, its hip cafés and craft-beer bars. Rocketing along an elevated track, I watched high-rises blur by, each a tiny honeycomb piece of the rail-linked urban megastructure that has recently erupted out of China’s landscape. China poured more concrete from 2011 to 2013 than America did during the entire 20th century. The country has already built rail lines in Africa, and it hopes to fire bullet trains into Europe and North America, the latter by way of a tunnel under the Bering Sea.

The skyscrapers and cranes dwindled as the train moved farther inland. Out in the emerald rice fields, among the low-hanging mists, it was easy to imagine ancient China—the China whose written language was adopted across much of Asia; the China that introduced metal coins, paper money, and gunpowder into human life; the China that built the river-taming system that still irrigates the country’s terraced hills. Those hills grew steeper as we went west, stair-stepping higher and higher, until I had to lean up against the window to see their peaks. Every so often, a Hans Zimmer bass note would sound, and the glass pane would fill up with the smooth, spaceship-white side of another train, whooshing by in the opposite direction at almost 200 miles an hour.

Liu Cixin, China’s preeminent science-fiction writer, has written a great deal about the risks of first contact. (Han Wancheng / Shanxi Illustration)
It was mid-afternoon when we glided into a sparkling, cavernous terminal in Guiyang, the capital of Guizhou, one of China’s poorest, most remote provinces. A government-imposed social transformation appeared to be under way. Signs implored people not to spit indoors. Loudspeakers nagged passengers to “keep an atmosphere of good manners.” When an older man cut in the cab line, a security guard dressed him down in front of a crowd of hundreds.
The next morning, I went down to my hotel lobby to meet the driver I’d hired to take me to the observatory. Two hours into what was supposed to be a four-hour drive, he pulled over in the rain and waded 30 yards into a field where an older woman was harvesting rice, to ask for directions to a radio observatory more than 100 miles away. After much frustrated gesturing by both parties, she pointed the way with her scythe.We set off again, making our way through a string of small villages, beep-beeping motorbike riders and pedestrians out of our way. Some of the buildings along the road were centuries old, with upturned eaves; others were freshly built, their residents having been relocated by the state to clear ground for the new observatory. A group of the displaced villagers had complained about their new housing, attracting bad press—a rarity for a government project in China. Western reporters took notice. “China Telescope to Displace 9,000 Villagers in Hunt for Extraterrestrials,” read a headline in The New York Times.

The search for extraterrestrial intelligence (seti) is often derided as a kind of religious mysticism, even within the scientific community. Nearly a quarter century ago, the United States Congress defunded America’s seti program with a budget amendment proposed by Senator Richard Bryan of Nevada, who said he hoped it would “be the end of Martian-hunting season at the taxpayer’s expense.” That’s one reason it is China, and not the United States, that has built the first world-class radio observatory with seti as a core scientific goal.

seti does share some traits with religion. It is motivated by deep human desires for connection and transcendence. It concerns itself with questions about human origins, about the raw creative power of nature, and about our future in this universe—and it does all this at a time when traditional religions have become unpersuasive to many. Why these aspects of seti should count against it is unclear. Nor is it clear why Congress should find seti unworthy of funding, given that the government has previously been happy to spend hundreds of millions of taxpayer dollars on ambitious searches for phenomena whose existence was still in question. The expensive, decades-long missions that found black holes and gravitational waves both commenced when their targets were mere speculative possibilities. That intelligent life can evolve on a planet is not a speculative possibility, as Darwin demonstrated. Indeed, seti might be the most intriguing scientific project suggested by Darwinism.Even without federal funding in the United States, seti is now in the midst of a global renaissance. Today’s telescopes have brought the distant stars nearer, and in their orbits we can see planets. The next generation of observatories is now clicking on, and with them we will zoom into these planets’ atmospheres. seti researchers have been preparing for this moment. In their exile, they have become philosophers of the future. They have tried to imagine what technologies an advanced civilization might use, and what imprints those technologies would make on the observable universe. They have figured out how to spot the chemical traces of artificial pollutants from afar. They know how to scan dense star fields for giant structures designed to shield planets from a supernova’s shock waves.
In 2015, the Russian billionaire Yuri Milner poured $100 million of his own cash into a new seti program led by scientists at UC Berkeley. The team performs more seti observations in a single day than took place during entire years just a decade ago. In 2016, Milner sank another $100 million into an interstellar-probe mission. A beam from a giant laser array, to be built in the Chilean high desert, will wallop dozens of wafer-thin probes more than four light-years to the Alpha Centauri system, to get a closer look at its planets. Milner told me the probes’ cameras might be able to make out individual continents. The Alpha Centauri team modeled the radiation that such a beam would send out into space, and noticed striking similarities to the mysterious “fast radio bursts” that Earth’s astronomers keep detecting, which suggests the possibility that they are caused by similar giant beams, powering similar probes elsewhere in the cosmos.Andrew Siemion, the leader of Milner’s seti team, is actively looking into this possibility. He visited the Chinese dish while it was still under construction, to lay the groundwork for joint observations and to help welcome the Chinese team into a growing network of radio observatories that will cooperate on seti research, including new facilities in Australia, New Zealand, and South Africa. When I joined Siemion for overnight seti observations at a radio observatory in West Virginia last fall, he gushed about the Chinese dish. He said it was the world’s most sensitive telescope in the part of the radio spectrum that is “classically considered to be the most probable place for an extraterrestrial transmitter.”
More on: https://www.theatlantic.com/magazine/archive/2017/12/what-happens-if-china-makes-first-contact/544131/

10 Things Children Born in 2018 Will Probably Never Experience

February 01, 2018

It’s All Coming Back to Me Now

2017 was a year filled with nostalgia thanks to a number of pop culture properties with ties to the past.

We got another official Alien film, and Blade Runner came back with new visuals to dazzle us. Meanwhile, “Stranger Things” hearkened back to the Spielbergian fantasy that wowed so many children of the ’80s, and “Twin Peaks” revived Agent Cooper so he could unravel yet another impenetrable mystery from the enigmatic mind of David Lynch.

As these films and TV shows remind us, a lot can change over the course of a few decades, and the experiences of one generation can be far different from those that follow closely behind thanks to advances in technology.

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While the “Stranger Things” kids’ phone usage reminded 30-somethings of their own pre-mobile adolescences, children born in 2018 will probably never know the feeling of being tethered to a landline. A trip to the local megaplex to catch Blade Runner 2049 may have stirred up adults’ memories of seeing the original, but children born this year may never know what it’s like to watch a film on a smaller screen with a sound system that doesn’t rattle the brain.

Technology is currently advancing faster than ever before, so what else will kids born today only read about in books or, more likely, on computer screens? Here’s a list of the top 10 things that children born in 2018 will likely never experience.

Long, Boring Travel

Mobile devices and in-flight entertainment systems have made it pretty easy to stay distracted during the course of a long trip. However, aside from the Concorde, which was decommissioned in 2003, humanity hasn’t done nearly as much to increase the speed of air travel for international jet-setters. Beyond sparsely utilized bullet trains, even the speed of our ground transportation has remained fairly limited.

However, recent developments in transportation will likely speed up the travel process, meaning today’s kids may never know the pain of seemingly endless flights and road trips.

Supersonic planes are making a comeback and could ferry passengers “across the pond” in as few as 3.5 hours. While these aircraft could certainly make travel faster for a small subset of travelers, physical and cost limitations will likely prevent them from reaching the mainstream.

However, hyperloop technology could certainly prove to be an affordable way for travelers to subtract travel time from their itineraries.

Already, these super-fast systems have the ability to travel at speeds up to 387 kmh (240 mph). If proposed routes come to fruition, they could significantly cut the time of travel between major cities. For example, a trip from New York to Washington D.C. could take just 30 minutes as opposed to the current five hours.

Driver’s Licenses

Obtaining a driver’s license is currently a rite of passage for teenagers as they make that transition from the end of childhood to the beginning of adulthood. By the time today’s newborns are 16, self-driving cars may have already put an end to this unofficial ritual by completely removing the need for human operators of motor vehicles.

According to the Centers for Disease Control (CDC), an average of six teens between the ages of 16 and 19 died every day in 2015 from injuries sustained in motor vehicle collisions. Since a vast majority of accidents are caused by human error, removing the human from the equation could help to save the lives of people of all ages, so autonomous cars are a serious priority for many.

Elon Musk, CEO of Tesla, is confident that his electric and (currently) semi-autonomous car manufacturing company will produce fully autonomous vehicles within the next two years, and several ride-hailing services are already testing self-driving vehicles.

Biology’s Monopoly on Intelligence

Self-driving cars are just a single example of innovations made possible by the advancement of artificial intelligence (AI).

Today, we have AI systems that rival or even surpass human experts at specific tasks, such as playing chess or sorting recyclables. However, experts predict that conscious AI systems that rival human intelligence could just be decades away.

Advanced robots like Hanson Robotics’ Sophia are already blurring the line between humanity and machines. The next few decades will continue to push boundaries as we inch closer and closer to the singularity.

Children born in 2018 may never know what it’s like to join the workforce or go to college at a time when humans are the smartest entities on the planet.

Language Barriers

Another promising use for AI is communication, and eventually, technology could end the language barrier on Earth.

Communication tools such as Skype have already incorporated instantaneous translating capabilities that allow speakers of a few languages to freely converse in real-time, and Google has incorporated translating capabilities into their new headphones.

Other companies, such as Waverly Labs, are also working on perfecting the technology that will eventually rival the ability of the Babel fish, an alien species found in the book “The Hitchhiker’s Guide to the Galaxy” that can instantly translate alien languages for its host.

Children born in 2018 may find themselves growing up in a world in which anyone can talk to anyone, and the idea of a “foreign” language will seem, well, completely foreign.

Humanity as a Single-Planet Species

Technology that improves human communication could radically impact our world, but eventually, we may need to find a way to communicate with extraterrestrial species. Granted, the worlds we reach in the lifetimes of anyone born this year aren’t likely to contain intelligent life, but the first milestones on the path to such a future are likely to be reached in the next few decades.

When he’s not ushering in the future of autonomous transportation, Musk is pushing his space exploration company SpaceX to develop the technology to put humans on Mars. He thinks he’ll be able to get a crew to the Red Planet by 2024, so today’s children may have no memory of a time before humanity’s cosmic footprint extended beyond a single planet.

Quiet Spaces

Overpopulation is one of the factors that experts point to when they discuss the need for humanity to spread into the cosmos. Urban sprawl has been an issue on Earth for decades, bringing about continued deforestation and the elimination of farming space.

A less-discussed problem caused by the continuous spread of urbanization, however, is the increase in noise pollution.

Experts are concerned that noise is quickly becoming the next great public health crisis. Data collected by the United Nations estimates that by 2100, 84 percent of the world’s 10.8 billion citizens will live in cities, surrounded by a smorgasbord of sound.

This decline in the number of people who live in areas largely free from noise pollution means many of the babies born today will never know what it’s like to enjoy the sound of silence.

World Hunger

Urbanization may limit the space available for traditional farming, but thanks to innovations in agriculture, food shortages may soon become a relic of the past.

Urban farming is quickly developing into a major industry that is bringing fresh produce and even fish to many markets previously considered food deserts (areas cut off from access to fresh, unprocessed foods).

Vertical farming will bring greater access to underserved areas, making it more possible than ever to end hunger in urban areas. Meanwhile, companies are developing innovative ways to reduce food waste, such as by transforming food scraps into sweets or using coffee grounds to grow mushrooms.

If these innovations take hold, children born in 2018 could grow up in a world in which every person on Earth has access to all the food they need to live a healthy, happy life.

Paper Currency

The advent of credit cards may have been the first major blow to the utilization of cash, but it wasn’t the last. Today, paper currency must contend with PayPal, Venmo, Apple Pay, and a slew of other payment options.

By the time children born in 2018 are old enough to earn a paycheck, they will have access to even more payment options, and cash could be completely phased out.

In the race to dethrone paper currency, cryptocurrencies are a frontrunner. Blockchain technology is adding much needed security to financial transactions, and while the crypto market is currently volatile, experts are still optimistic about its potential to permanently disrupt finance.

Digital Insecurity

Today, digital security is a major subject of concern. Hacking can occur on an international level, and with the growth of the Internet of Things (IoT), even household appliances can be points of weakness in the defenses guarding sensitive personal information.

Experts are feverishly trying to keep security development on pace with the ubiquity of digitalization, and technological advances such as biometrics and RFID tech are helping. Unfortunately, these defenses still rely largely on typical encryption software, which is breakable.

The advent of the quantum computer will exponentially increase computing power, and better security systems will follow suit. By the time children born in 2018 reach adulthood, high-speed quantum encryption could ensure that the digital world they navigate is virtually unhackable.

Single-Screen Computing

While most of our digital devices currently make use of a typical flat screen, tomorrow’s user interfaces will be far more dynamic, and children born in 2018 may not remember a time when they were limited to a single screen and a keyboard.

The development of virtual reality (VR) and augmented reality (AR) have shifted the paradigm, and as these technologies continue to advance, we will increasingly see the incorporation of new capabilities into our computing experience.

Gesture recognition, language processing, and other technologies will allow for a more holistic interaction with our devices, and eventually, we may find ourselves interacting with systems akin to what we saw in Minority Report.