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.

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

These book reviews contain links to Amazon.com. Science News is a participant in the Amazon Services LLC Associates Program. Please see our FAQ for more details.

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.

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.

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.

Zika virus may not be the black sheep of the family. Infections with either of two related viruses also cause fetal defects in mice, researchers find.

Some scientists have speculated that Zika’s capacity to harm a fetus might be unique among its kind, perhaps due to a recent change in the virus’s genetic material (SN: 10/28/17, p. 9). Others have argued that perhaps this dangerous ability was always there. It just wasn’t until the 2015–2016 epidemic in the Western Hemisphere that enough pregnant women were affected for public health researchers to identify the association with fetal defects (SN: 12/24/16, p. 19).
But new work suggests this capacity is not Zika’s alone. Pregnant mice infected with West Nile or Powassan virus — both flaviviruses, like Zika — also showed fetal harm. Over 40 percent of these infected fetuses died. But among pregnant mice infected with one of two other mosquito-borne viruses unrelated to Zika, all of the fetuses survived, scientists report online January 31 in Science Translational Medicine.

The research underscores that “many viruses, including some similar to Zika, can infect the placenta and the cells of the baby,” says George Saade, an obstetrician-gynecologist and cell biologist at the University of Texas Medical Branch at Galveston. “This list keeps growing and highlights the risks from viruses that we are not very familiar with.”

Like Zika, West Nile virus and Powassan virus are neurotropic, meaning these pathogens target nerve cells. Both viruses can cause inflammation of the brain or of the membranes that surround the brain. West Nile is transmitted to humans by mosquitoes that have bitten infected birds. From 1999 to 2016, there were more than 46,000 cases reported to the U.S. Centers for Disease Control and Prevention. Powassan, spread by ticks who have fed on infected rodents, is less widespread; only 98 cases were reported from 2007 to 2016, mostly in the Northeast and Great Lakes area.

Jonathan Miner, a virologist at the Washington University School of Medicine in St. Louis, and his colleagues conducted some of the initial work in mice that demonstrated that Zika could harm fetuses (SN: 6/11/16, p. 15). The new study tests the effects of four other viruses: the two flaviviruses and two alphaviruses, chikungunya and Mayaro, which also have led to outbreaks in Zika-affected areas.
The researchers infected 14 mice early in their pregnancies with one of the four viruses. By late pregnancy, 12 out of 30 fetuses from West Nile–infected mice had died, and half of the 16 fetuses from Powassan-infected mice had died. All of the fetuses from mice infected with chikungunya and Mayaro virus survived. West Nile virus and Powassan virus also replicated, or multiplied, more efficiently than the alphaviruses in lab samples of human placental tissue.

Zika, West Nile and Powassan share similarities in their genetic information, Miner says. “So there may be certain features of those virus genes and proteins in that particular family that confers this ability to infect certain cell types.” But scientists don’t understand fully what those features are yet, he says.

While this is the first study comparing the effects in mice of these mosquito-transmitted and tick-transmitted viruses in parallel, Miner says, past studies have raised the possibility of fetal infections with other flaviviruses besides Zika. A 2006 study of 77 pregnant women infected with West Nile virus reported that two had infants with microcephaly, the birth defect lately associated with Zika that results in unusually small and damaged brains.

In general, examining the potential effects of other flaviviruses on pregnant women and their developing fetuses is difficult, because outbreaks have been sporadic and less widespread than with Zika. It’s possible that cases in humans “could go largely unnoticed if we don’t look for them,” Miner says.

A new blood test might reveal whether someone is at risk of getting Alzheimer’s disease.

The test measures blood plasma levels of a sticky protein called amyloid-beta. This protein can start building up in the brains of Alzheimer’s patients decades before there’s any outward signs of the disease. Typically, it takes a brain scan or spinal tap to discover these A-beta clumps, or plaques, in the brain. But evidence is growing that A-beta levels in the blood can be used to predict whether or not a person has these brain plaques, researchers report online January 31 in Nature.
These new results mirror those of a smaller 2017 study by a different team of scientists. “It’s a fantastic confirmation of the findings,” says Randall Bateman, an Alzheimer’s researcher at Washington University School of Medicine in St. Louis, who led the earlier study. “What this tells us is that we can move forward with this [test] approach with fairly high confidence that this is going to pan out.”

There’s currently no treatment for Alzheimer’s that can slow or stop the disease’s progression, so catching it early can’t currently improve a patient’s outcome. But a blood test could help researchers more easily identify people who might be good candidates for clinical trials of early interventions, says Steven Kiddle, a biostatistician at the University of Cambridge, who wasn’t part of either study.

Creating such a test has been challenging: Relatively little A-beta floats in the bloodstream compared with how much accumulates in the brain. And many past studies haven’t found a consistent correlation between the two.

In the new study, researchers used mass spectrometry, a more sensitive measuring technique than used in most previous tests, which allowed the detection of smaller amounts of the protein. And instead of looking at the total level of the protein in the blood, the team calculated the ratios between different types of A-beta, says coauthor Katsuhiko Yanagisawa, a gerontologist at the National Center for Geriatrics and Gerontology in Obu, Japan.
He and his colleagues analyzed brain scans and blood samples from a group of 121 Japanese patients and a group of 252 Australian patients. Some participants had Alzheimer’s, some didn’t, and some had mild cognitive impairments that weren’t related to Alzheimer’s.

Using the ratios, the researchers found that they could discriminate between people who had A-beta plaques in the brain and those who didn’t. A composite biomarker score, created by combining two different ratios, predicted the presence or absence of A-beta plaques in the brain with about 90 percent accuracy in both groups of patients, the researchers found.

The new results are promising, Kiddle says, but the test still needs more refining before it can be used in the clinic. Another wild card: the cost. It’s still not clear whether the blood test will be more affordable than a brain scan or a spinal tap.