Approval of gene therapies for two blood cancers led to an ‘explosion of interest’ in 2017

This year, gene therapy finally became a clinical reality. The U.S. Food and Drug Administration approved two personalized treatments that engineer a patient’s own immune system to hunt down and kill cancer cells. The treatments, the first gene therapies ever approved by the FDA, work in people with certain blood cancers, even patients whose cancers haven’t responded to other treatments.

Called CAR-T cell immunotherapy (for chimeric antigen receptor T cell), one is for kids and young adults with B cell acute lymphoblastic leukemia, or ALL, approved in August (SN Online: 8/30/17). The other is for adults with non-Hodgkin lymphoma, approved in October. Other CAR-T cell therapies are in testing, including a treatment for multiple myeloma.
“It’s a completely different way of treating cancer,” says pediatric oncologist Stephan Grupp, who directs the Cancer Immunotherapy Program at the Children’s Hospital of Philadelphia. Grupp spearheaded the clinical trials of the newly approved ALL therapy, called Kymriah.

Researchers are developing many different versions of CAR-T cell therapies, but the basic premise is the same: Doctors remove a patient’s T cells (immune system cells that attack invaders) from a blood sample and genetically modify them to produce artificial proteins on their surfaces. Those proteins, called chimeric antigen receptors, recognize the cancer cells in the patient’s body. After the modified T cells make many copies of themselves in the lab, they’re unleashed in the patient’s bloodstream to find and kill cancer cells.
CAR-T cell therapy is particularly exciting because it works well in people whose cancers haven’t responded to other available treatments, says Renier Brentjens, an oncologist at Memorial Sloan Kettering Cancer Center in New York City. Of the 63 kids and young adults treated in a clinical trial of Kymriah, 83 percent had their cancers go into remission within three months.
Now that these therapies have been clinically approved, there’s been an “explosion of interest” in the approach, says Dario Campano, an immunopathologist at the National University Cancer Institute in Singapore. Going forward, he expects to see even more rapid progress in the technology. Fifteen years ago, Campana helped develop the chimeric antigen receptor that’s used in Kymriah today. For now, the treatments are approved for use only when other treatments have failed, but someday CAR-T cell therapy could be the first treatment doctors try, he says.

One drawback is the price. Kymriah costs $475,000 for a onetime treatment, according to Novartis, which makes Kymriah. The non-Hodgkin lymphoma treatment made by Gilead Sciences, called Yescarta, is listed at $373,000. The total price tag for treatment could be higher when the costs of dealing with side effects and complications are factored in.

The approach is approved only for blood cancers. Using CAR-T cell therapy on solid tumors will require finding ways to get the T cells past additional cellular roadblocks, Grupp says.

Here are our favorite science books of 2017

Have you fallen behind on your reading this year? Or maybe you’ve plowed through your must-reads and are ready for more. Science News has got you covered. Here are the staff’s picks for some of the best science books of 2017. Find detailed reviews from previous issues in the links below or in our Editors pick: Favorite books of 2017.

Against the Grain
James C. Scott

Armed with the latest archaeological research, a political anthropologist argues that the rise of civilization came at a big cost. The initial switch from hunting and gathering to agricultural states brought poor diets, labor-intensive work, outbreaks of infectious diseases and other hardships (SN: 10/14/17, p. 28). Yale Univ., $26

The Great Quake
Henry Fountain

Historical records and interviews with survivors flesh out this tale of how a massive earthquake in Alaska in 1964 provided geologists with key evidence needed to verify the theory of plate tectonics (SN: 9/16/17, p. 32). Crown, $28

Eclipse
Frank Close

More than just a primer on the science of solar eclipses, this memoir chronicles a physicist’s lifetime fascination with the celestial phenomenon and introduces readers to the quirky world of eclipse chasers (SN: 5/13/17, p. 28). Oxford Univ., $21.95

Rise of the Necrofauna
Britt Wray

Resurrecting woolly mammoths, passenger pigeons and other extinct creatures isn’t just a technological problem, as this book explains. “De-extinction” is also rife with ethical dilemmas (SN: 10/28/17, p. 28). Greystone Books, $26.95

Big Chicken
Maryn McKenna

Antibiotics transformed chicken farming, to the detriment of the birds and of human health, a journalist contends. Widespread use of the drugs fueled the industrialization of poultry production and the rise of antibiotic-resistant bacteria (SN: 9/30/17, p. 30). National Geographic, $27

Inferior
Angela Saini

A science writer makes a persuasive case that centuries of biased thinking and flawed scientific research have reinforced sexist stereotypes about women (SN: 9/2/17, p. 27). Beacon Press, $25.95

Caesar’s Last Breath
Sam Kean

Through fun historical anecdotes and lesser-known backstories of scientific greats, this entertaining book profiles the chemical elements that make up the air we breathe and traces the history of Earth’s atmosphere (SN: 7/8/17 & 7/22/17, p. 38). Little, Brown and Co., $28

Cannibalism
Bill Schutt

The grisly practice of eating your own kind turns out to be widespread in the animal kingdom, a zoologist explains in this captivating look at cannibalism (SN: 2/18/17, p. 29). Algonquin Books, $26.95

The Lost City of the Monkey God
Douglas Preston

A journalist tags along on an archaeological expedition to search for the real-life remains of a mythological city in this rainforest adventure tale that morphs into a medical mystery (SN: 2/4/17, p. 28). Grand Central Publishing, $28

The Death and Life of the Great Lakes
Dan Egan

Invasive species, urbanization and other threats have wreaked havoc on the Great Lakes, but this book still finds some glimmers of hope in the scientists who are making headway in resuscitating the ecosystem (SN: 3/18/17, p. 30). W.W. Norton & Co., $27.95

How to Tame a Fox
Lee Alan Dugatkin and Lyudmila Trut

An experiment to replay animal domestication by selectively breeding wild silver foxes is lovingly retold, including by the researcher who has kept the project alive for nearly 60 years (SN: 5/13/17, p. 29). Univ. of Chicago, $26

Making Contact
Sarah Scoles

In the face of numerous obstacles, Jill Tarter still managed to spearhead the search for extraterrestrial intelligence for decades, as this biography recounts (SN: 8/5/17, p. 26). Pegasus Books, $27.95

A Crack in Creation
Jennifer A. Doudna and Samuel H. Sternberg

Two experts, including one of the pioneers of CRISPR/Cas9, discuss the science and ethics of gene editing. Houghton Mifflin Harcourt, $28

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U.S. life expectancy drops for the second year in a row

Life expectancy in the United States has decreased for the second year in a row, the first back-to-back drops in more than 50 years, the U.S. Centers for Disease Control and Prevention reports.

In 2016, life expectancy at birth was 78.6 years for the U.S. population as a whole. That’s 0.1 year less than in 2015. For men, life expectancy decreased from 76.3 years in 2015 to 76.1 years in 2016, while in women it remained the same, at 81.1 years. The new data, from CDC’s National Center for Health Statistics, are published online December 21.
Heart disease was the leading cause of death for 2016, followed by cancer, unintentional injuries such as drug overdoses and car crashes, chronic lower respiratory diseases including asthma, and stroke. Rounding out the top 10 causes of death were Alzheimer’s disease, diabetes, influenza and pneumonia, kidney disease and suicide.

The overall drop in life expectancy is largely a result of an uptick in the age-adjusted death rates for unintentional injuries, Alzheimer’s disease and suicide, the report’s authors say.

Volume of fracking fluid pumped underground tied to Canada quakes

Fracking wells should not go to 11. Instead, turning down the volume — that is, of water pumped underground to help retrieve oil and gas — may reduce the number of earthquakes related to hydraulic fracturing.

The amount of water pumped into fracking wells is the No. 1 factor related to earthquake occurrence at Fox Creek, a large oil and gas production site in central Canada, researchers report January 19 in Science. An injection of 10,000 cubic meters of fluid or more at a well appears to trigger a quake.
Fox Creek sits atop the Duvernay Formation, a sedimentary layer rich in oil and gas. Before December 2013, the area was earthquake-free. Since then, hundreds of earthquakes have shaken the region; most were below magnitude 4, but a magnitude 4.8 quake in 2016 temporarily shut down operations.

Previous investigations revealed that fracking well injections at the site were triggering earthquakes on an underlying fault system. But mysteries remained: For example, why didn’t the quakes didn’t start until almost three years after fracking activities began in 2010?

Ryan Schultz of the Alberta Geological Survey in Edmonton and his colleagues compared the timing and location of the earthquakes with fracking activity at 300 wells in the region.

An analysis of rates of injection, fluid pressure and fluid volume for the wells closest in proximity to the quakes revealed that, at this site, only volume was linked to the quakes. A previous study has linked the rate of wastewater disposal injections to seismic slip (SN: 7/11/15, p. 10).
As for the three-year delay, the authors say, fracking well injections tend to increase in volume over time as operations mature. So once the injection volumes reached that 10,000-cubic- meter threshold, the earthquakes began.

Scientists find 10 new defense systems used by bacteria

Since long before it gained fame as a precise gene-editing tool, CRISPR has had another job defending bacteria against viral invaders. And it’s far from alone. Ten sets of bacterial genes have similar, newly discovered defense roles, researchers report online January 25 in Science.

The discovery “probably more than doubles the number of immune systems known in bacteria,” says Joseph Bondy-Denomy, a microbiologist at the University of California, San Francisco, who wasn’t involved in the study.
Bacteria are vulnerable to deadly viruses called phages, which can hijack bacteria’s genetic machinery and force them to produce viral DNA instead. Some bacteria protect themselves against phage attacks with a system called CRISPR, which stores pieces of past invaders’ DNA so bacteria can recognize and fend off those phages in the future (SN: 4/15/17, p. 22). But only about 40 percent of bacteria have CRISPR, says study coauthor Rotem Sorek, a microbial genomicist at the Weizmann Institute of Science in Rehovot, Israel. That’s why he and his colleagues are hunting for other defense mechanisms.

Defense-related genes tend to cluster together in the genome, Sorek says. So his team sifted through genetic information from 45,000 microbes, flagging groups of genes with unknown functions that were located near known defense-related genes.

Many of the bacteria with these gene families hail from far-flung locations like the bottom of the ocean. So the researchers used the genomic data to synthesize the relevant bits of DNA and inserted them into Escherichia coli and Bacillus subtilis, which can both be grown and studied in the lab. Then, the researchers tracked how well the bacteria resisted phage attacks when various genes in a family were deleted. If getting rid of some of the genes affected the bacteria’s ability to fight off phages, that result suggested the group of genes was a defense system.

Nine groups of bacterial genes turned out to be antiphage defense systems, and one system protected against plasmids, another source of foreign DNA, the researchers found.
Previously discovered antiphage protective systems, such as CRISPR, have been described with acronyms, but, Sorek jokes, “we ran out of acronyms.” So the new systems are named after protective deities — like the Zorya, a pair of goddesses from Slavic mythology.

The data also reveal a possible shared origin between bacterial immune systems and similar defenses in more complex organisms, Sorek says. Some of the genes contained fragments of DNA that are also known to be an important part of the innate immune system in plants, mammals and invertebrates.

It’s likely the research will unleash a flurry of new studies to figure out how these new defense systems work and whether they, like CRISPR, might also be useful biotechnology tools, Bondy-Denomy predicts.

Knotted structures called skyrmions seem to mimic ball lightning

The physics behind a weird electrical phenomenon — glowing orbs of lightning — may be mimicked by something even stranger. A magnetic structure proposed for the natural oddity known as ball lightning makes an appearance in a newfound variety of a knotlike entity called a skyrmion, a team of scientists reports.

Typically observed during thunderstorms, ball lightning is poorly understood. Anecdotal reports describe eerily glowing spheres that float through the air for several seconds before fading (SN: 2/9/02, p. 87). That’s much longer than standard lightning strikes, which last tens of microseconds, and researchers are still struggling to explain how the fireballs persist.
One theory, proposed in the 1990s, suggests that ball lightning is a plasma held together by magnetic fields arranged in rings that link together into a knot. “Because it’s linked up in this tight way, it can’t really fall apart,” says physicist David Hall of Amherst College in Massachusetts. “That could provide a reason why ball lightning survives as long as it does.”
Now, Hall and colleagues have created an analog of such linked magnetic fields in a seemingly unrelated type of knotted structure, a skyrmion. Found in a variety of substances — from thin films of magnetic materials to liquid crystals — skyrmions are a kind of disturbance within matter
( SN: 2/17/18, p. 18 ). The objects can move like independent particles , shifting from place to place within a material while maintaining their knotted configuration ( SN: 10/18/14, p. 22 ). And like a tight knot in a thread, skyrmions are difficult to undo, making them relatively stable structures.
Hall and colleagues created their skyrmion in a state of matter called a Bose-Einstein condensate, composed of atoms cooled to a temperature so low that they all take on the same quantum state and begin acting as if they are one unified entity (SN: 10/13/01, p. 230). The atoms that make up the Bose-Einstein condensate each have a quantum property called spin, which makes them behave like tiny magnets.

When the scientists switched on a specially designed magnetic field, the spins arranged into a twisting structure of loops, knotting up into a configuration known as a Shankar skyrmion. That arrangement was predicted theoretically about 40 years ago, but not seen in the real world until now. While skyrmions found in thin magnetic materials are two-dimensional whirls, the new skyrmion is a 3-D beast, the researchers report March 2 in Science Advances.

Within the condensate, the spins produced something analogous to a magnetic field: The condensate behaved as if it were a charged particle being pushed around by a magnetic field when in reality no such magnetic field existed. Like the skyrmion itself, the scientists realized, the imitation magnetic field was knotted, and it matched the interlinked rings of magnetic fields proposed for ball lightning.

Eventually, studying 3-D knotted magnetic fields like those potentially present in ball lightning might help scientists devise better ways to control plasmas within future fusion reactors for generating power, the researchers suggest.

The creation of knotted structures in Bose-Einstein condensates is in its infancy, and such efforts are “very welcomed” says physicist Egor Babaev of KTH Royal Institute of Technology in Stockholm, who was not involved with the research. “People are just starting to scratch the surface of these objects.”

We probably won’t hear from aliens. But by the time we do, they’ll be dead.

If signals from an alien civilization ever reach Earth, odds are the aliens will already be dead.

In an effort to update the 1961 Drake Equation, which estimates the number of detectable, intelligent civilizations in the Milky Way, physicist Claudio Grimaldi and colleagues calculated the area of the galaxy that should be filled with alien signals at a given time (SN Online: 11/1/09).

The team, which includes Frank Drake (now a professor emeritus at the SETI Institute in Mountain View, Calif., and the University of California, Santa Cruz), assumed technologically savvy civilizations are born and die at a constant rate. When a civilization dies out and stops broadcasting, the signals it had sent continue traveling like concentric ripples on a pond. Part of the Milky Way should be filled with these ghost signals.
If the civilization lasted less than 100,000 years — the time it takes light to cross the galaxy — then the odds of the signals reaching Earth while the civilization is still broadcasting are vanishingly small, the researchers report February 27 at arXiv.org. Humans, for example, have been transmitting radio waves for only about 80 years, so our radio waves cover less than 0.001 percent of the Milky Way.

“If the civilization emitted from the other side of the galaxy, when the signal arrives here, the civilization will already be gone,” says Grimaldi, of the Federal Polytechnical School of Lausanne in Switzerland.

Surprisingly, the team also calculated that the average number of E.T. signals crossing Earth at a given time should equal the number of civilizations currently transmitting — even if the civilizations we hear from aren’t the same ones presently broadcasting. Grimaldi is now working on a paper about what it means that we’ve found none so far.