Lung Cancer Patients Live Longer With Immune Therapy

Odds of survival can greatly improve for people with the most common type of lung cancer if they are given a new drug that activates the immune system along with chemotherapy, a major new study has shown.

The findings, medical experts say, should change the way doctors treat lung cancer: Patients with this form of the disease should receive immunotherapy as early as possible.

“What it suggests is that chemotherapy alone is no longer a standard of care,” said Dr. Leena Gandhi, a leader of the study and director of the Thoracic Medical Oncology Program at the Perlmutter Cancer Center at New York University Langone Health.

Immunotherapy has been making steady gains against a number of cancers. Four such drugs, called checkpoint inhibitors, which unleash the patient’s own immune system to kill malignant cells, have been approved so far.

They cost more than $100,000 a year, can have serious side effects and help only some patients, generally fewer than half. But when the drugs work, responses can be long-lasting, and researchers are rushing to find ways to combine treatments to improve their effects and to determine which formulation is best for each patient.

“I’ve been treating lung cancer for 25 years now, and I’ve never seen such a big paradigm shift as we’re seeing with immunotherapy,” said Dr. Roy Herbst, Chief of Medical Oncology at the Yale Cancer Center. He was not involved in the pembrolizumab study.

Lung cancer is the leading cause of cancer death globally, causing 1.7 million deaths a year. In the United States, it is expected to kill more than 154,000 people in 2018.

Patients in the study had an advanced stage of non-squamous non-small-cell lung cancer. The immune-activating drug was a checkpoint inhibitor called pembrolizumab, or Keytruda, made by Merck, which paid for the study. The chemotherapy was a drug called pemetrexed, plus either carboplatin or cisplatin.

Dr. Gandhi said chemotherapy alone had only a “modest benefit,” and could add only a few months of life, with most patients surviving about a year or less. The combination treatment is a significant improvement, she said. It is already approved as a first-line treatment for this disease, so it should be covered by health insurers.

She was scheduled to present the results on Monday in Chicago at a meeting of the American Association for Cancer Research, and they were also published in The New England Journal of Medicine.

Other studies presented at the meeting also highlighted advances in immunotherapy against lung cancer, but were at earlier points in the research and less likely to bring about immediate changes in medical practice.

“If you want to see long-term survival, you’ve got to give immunotherapy as soon as possible,” Dr. Herbst said. “Chemotherapy has limitations. Immunotherapy has the ability to cure. I lead the Yale lung team. We have patients on these immunotherapies alive more than eight years.”

Other studies in lung cancer have involved another checkpoint inhibitor, nivolumab, or Opdivo (made by Bristol-Myers Squibb), which works in a similar way to pembrolizumab. The data are not conclusive, but Dr. Herbst said, “In lung cancer, my suspicion is these drugs are the same, like Coke vs. Pepsi.”

Most patients stay on the drugs for two years, he said. One Yale patient who has survived for eight years took the drug for two years and has remained well ever since. Another had to stop because of side effects after two or three months, but is well two years later.

Dr. Herbst offered several theories about why chemotherapy and immunotherapy could work well together. He said that tumor cells were like bags of hidden proteins that, if exposed, the immune system could use as targets to find and attack cancer. By killing some tumor cells, chemotherapy could pop open the bags, release the contents and help immune cells — unleashed by the checkpoint drugs — to identify their prey. It is also possible, he said, that chemotherapy may kill some immune cells that interfere with the cancer-killing action of other parts of the immune system.

Dr. Gandhi’s study included 616 patients with advanced lung cancer, ages 34 to 84, from medical centers in 16 countries. Their tumors lacked certain mutations that would have made them eligible for other, so-called “targeted” treatments. They were picked at random to receive either chemotherapy plus immunotherapy, or chemotherapy plus a placebo, with two thirds receiving the combination that included immunotherapy.

After a median follow-up of 10.5 months, those in the immunotherapy group were half as likely to die. The median overall survival was 11.3 months in those who did not receive immunotherapy, whereas survival in the immunotherapy group was longer and the median has not yet been reached.

But patients in the immunotherapy group had more kidney problems, more immune-related adverse events and were more likely to stop treatment because of side effects.

The estimated survival at 12 months was 69.2 percent in the group that received immunotherapy, and 49.4 percent in those who did not.

“I think we were all surprised at the magnitude of benefit and how clear the difference was at an early analysis, and that we could tell there was an overall survival difference,” Dr. Gandhi said, adding that there was “a lot of excitement” at the conference about her study and several others involving immunotherapy.

“It represents a sea change in the way we think about treating lung cancer,” she said. “All of it is better than what we’ve been using for years. Going forward, it will only get better.”

Patients were tested for a biomarker used to predict whether pembrolizumab is likely to help them. The drug alone is already approved to treat patients with high levels of those markers. But this study included patients with varying levels. Those with high levels of the marker fared somewhat better with immunotherapy than those with low levels — but even those with low levels were helped.

“The data are impressive,” Dr. Herbst said. “We’re making progress, but still only benefiting 30 to 40 percent of patients. There’s a lot more room to do better. We have to keep looking for new things and new approaches.”


This article was originally published in The New York Times.  Read the original article.

A Scientist’s Mission: Talking Genetics With Everybody

Ting Wu, a professor at Harvard Medical School, fields lots of questions at the public meetings and workshops that she helps to run on recent advances in genetics. Should scientists, for example, have the right to run experiments that create heritable genetic changes in embryos, sperm or eggs? Or, is it too risky to the environment to use genetic technology to try to eradicate a species of disease-carrying mosquito?

Dr. Wu is eager to help non-scientists understand the complexities—and to hear their concerns. “That’s why we are here,” she says.

As one of the co-founders of the Personal Genetics Education Project, Dr. Wu, 64, has promoted the need for wider discussion about her field—beyond the closed doors of scientists’ labs—for more than a decade. Today, she says, informed public discussion of genetics is more urgent than ever before.

Rapid advances in gene-editing technology—especially Crispr-Cas9, a tool that allows scientists to insert, modify or delete genes not only in an individual’s DNA but potentially in the DNA of future generations—gives scientists tremendous power to change the way that life progresses. “All people need to have a voice in how genetics is used,” Dr. Wu says.

In recent years, Dr. Wu and her organization’s small team of teachers, scientists and community activists have stepped up their efforts to raise awareness and spark dialogue. They have focused on communities that often end up getting left out of conversations about genetic technology—people of color and faith and those who live in rural areas.

The group usually operates from Dr. Wu’s own research lab, where she works on chromosome organization and behavior and tools for visualizing the genome. But it recently launched a new community-based initiative, setting up an office in Fields Corner, a multicultural neighborhood of Boston. Staff members meet and talk to people in their schools, community centers and places of worship. Last year, the project, working with the Minority Coalition for Precision Medicine, sponsored a conference at Harvard with pastors, faith leaders and scientists to discuss the ethics of genome editing.

Genetics has to be open to everyone.

People raise confounding ethical dilemmas in all of these discussions, says Dr. Wu. Do you have an obligation to share the results of genetic testing with other members of your family? Is it moral to use genetic information to make life decisions for yourself or your children when so much remains uncertain about interpreting genetic results?

“Genetics is so personal,” says Dr. Wu. “But it is also incredibly intertwined with family and community and our most important relationships.”

That is also how Dr. Wu describes her own path into science. Her father, Nelson Ikon Wu, was a renowned art historian, teaching Asian art and architecture. Dr. Wu grew up in New Haven, Conn., and St. Louis, where her father held university posts. She loved art and in college initially considered pursuing sculpture or print-making.

But she also had a longstanding interest in genetics, sparked by her mother, Mu-lien H. Wu, a researcher in the field. To help pay for her studies at Radcliffe College, Dr. Wu took a job washing glassware in a genetics lab. One evening, a scientist running an experiment needed an extra pair of hands and asked her to help measure out liquids. “I loved it,” she says.

She was soon majoring in biology and spending all of her free time in the lab, working late into the night on experiments before falling asleep on a cot in the women’s restroom. The head of the lab found someone else to wash the glassware and hired Dr. Wu as a research assistant.

She sees a connection between her interests in genetics and art: Both involve trying to recognize patterns, even unexpected ones. “It is very aesthetically pleasing,” she says.

Studying for a Ph.D. in genetics at Harvard Medical School, Dr. Wu met her future husband, George Church. The couple frequented the library and took long walks discussing their shared scientific passions. In recent years, many of their conversations have touched on Crispr. Dr. Church and his lab at Harvard were among the first to demonstrate how to use the Crispr tool to edit human cells, and he has helped found several Crispr companies.

Dr. Wu says that even now, she likes nothing better than to stay up late with friends and family, cooking and talking about science. She and Dr. Church share an adjoining backyard with their grown daughter, her husband and their two children. When the grandchildren come over, Dr. Wu says, “everything else stops.”

In the summer of 2006, Dr. Wu, Dr. Church and their daughter, then age 14, set out on a 2,000-mile road trip across the U.S. and Canada. Dr. Church had just started the Personal Genome Project, which aimed to collect the medical records of volunteers and sequence their genomes, and then to put the data online. The couple was worried that people might not understand the ethical implications of the technology, so they took the trip to meet and talk with some of the early volunteers.

When she and Dr. Church returned to Harvard, Dr. Wu and two collaborators founded the education project. “The idea was to listen,” she says. Genetic technology has changed a great deal over the past decade, but her goal has not, Dr. Wu says. “Genetics has to be open to everyone.”


This article was originally published in The Wall Street Journal. Read the original article.

New York Mice Are Crawling With Dangerous Bacteria and Viruses

Mice that live in the basements of New York City apartment buildings — even at the most exclusive addresses — carry disease-causing bacteria, antibiotic-resistant bugs and viruses that have never been seen before, a new study from Columbia University finds.

Researchers collected feces from more than 400 mice captured over a year in eight buildings in Manhattan, Brooklyn, Queens and the Bronx. The team then analyzed the droppings for bacteria and viruses.

The viruses included nine species that had never been seen before and others that have not been known to cause human disease, according to the study, published Tuesday in the journal mBio.

But in a second study focused on bacteria, the researchers detected some of the most recognizable disease-causing pathogens, including Shigella, Salmonella, Clostridium difficile and E. coli. The scientists also found antibiotic-resistant bacteria like those that have become nearly untreatable at area hospitals.

It’s unclear whether the bacteria on the mice pose any health threat to people or have caused any human disease. But for centuries, rodents have been linked to illnesses like the Black Death.

“They are a potential source of human infection,” said Dr. W. Ian Lipkin, the epidemiologist at the Mailman School of Public Health at Columbia who was the senior author on the study. “The real message is that these things are everywhere.”

The mice appeared to be healthy, and Dr. Lipkin said he presumes that they are carriers of the bacteria but are not affected by them.

Dr. Lipkin said it was not clear whether the mice were getting the antibiotic-resistant bacteria from people — say, by eating food contaminated with the feces of someone taking antibiotics — or whether the bacteria developed resistance after mice ate discarded antibiotics.

It would be nearly impossible to conduct research directly linking a mouse pathogen with a human disease, said Charles Calisher, a professor emeritus at Colorado State University, who was not involved in the new studies.

The source of patients’ infections are rarely investigated, and they are not usually asked about their contact with mice, he said. “These are not simple things to investigate,” Dr. Calisher said.

Peter Daszak, who heads the EcoHealth Alliance, a nonprofit that researches emerging diseases around the world, also described the research as difficult.

It’s crucial to identify and trace these microbes, he said, to help understand how they are transmitted and how, if necessary, to protect ourselves from the diseases they may carry.

“If we don’t know where they originate, we can’t identify what’s driving them and then we can’t control it,” said Dr. Daszak, who was not involved in the research.

No one knows, for example, whether antibiotic resistance genes emerged in hospitals, in cities or in rural areas.

This research is particularly important to do in New York, Dr. Daszak said, because the city is a destination for people from all corners of the world.

“New York is a major at-risk place for pathogens,” he said. “We’re certainly on the front line for emerging diseases.”

He said that the new research should not make New Yorkers more fearful of mice. “I’m not worried personally,” said Dr. Daszak, who lives in suburban Rockland County but works in the city. “Luckily, this is a species we’re already trying to control.”

Dr. Lipkin began researching New York City’s natural pathogens after the terrorist attacks of 9/11, when scientists realized they did not have a baseline to compare any changes. His lab has also studied rats on the New York City subway system and found many of the same infectious bacteria.

Although it is impossible to completely get rid of urban mice, Dr. Lipkin said his study suggests that more should be done to control mouse populations and their interactions with people.

Large apartment buildings should fill any gaps in their foundations, and trap and control any rodents found indoors, Dr. Calisher said.

Should everybody get a cat? “Cats have their own viruses,” Dr. Calisher noted.


This article was originally published in The New York Times.  Read the original article.

Bodies Remodeled for a Life at Sea

We are the products of evolution, and not just evolution that occurred billions of years ago. As scientists peer deeper into our genes, they are discovering instances of human evolution in just the past few thousand years.

People in Tibet and Ethiopian highlands have adapted to living at high altitudes, for example. Cattle-herding people in East Africa and northern Europe have gained a mutation that helps them digest milk as adults.

On Thursday in the journal Cell, a team of researchers reported a new kind of adaptation — not to air or to food, but to the ocean. A group of sea-dwelling people in Southeast Asia have evolved into better divers.

The Bajau, as these people are known, number in the hundreds of thousands, scattered in communities in Indonesia, Malaysia and the Philippines. They have traditionally lived on houseboats; in recent times, they’ve also built houses on stilts in coastal waters.

“They are simply a stranger to the land,” said Rodney C. Jubilado, a University of Hawaii anthropologist who studies the Bajau but was not involved in the new study.


The Bajau people number in the hundreds of thousands and live in houseboats and houses on stilts scattered across Indonesia, Malaysia and the Philippines. CreditMelissa Ilardo

Dr. Jubilado first encountered the Bajau while growing up on Samal Island in the Philippines. They made a living as divers, spearfishing or harvesting shellfish.

“We were so fascinated that they could stay underwater much longer than us local islanders,” Dr. Jubilado said. “I could see them literally walking under the sea.”

Even as anthropologists study Bajau culture, biologists have grown curious about them, too. Bajau divers been observed plunging more than 200 feet underwater, their only protection a pair of wooden goggles — a physiological marvel.

In 2015, Melissa Ilardo, then a graduate student in genetics at the University of Copenhagen, heard about the Bajau. She wondered if centuries of diving could have led to the evolution of traits that made the task easier for them.

“It seemed like the perfect opportunity for natural selection to act on a population,” said Dr. Ilardo.

Her first step was to travel to Sulawesi, Indonesia, and then to a coral reef island where she reached a Bajau village. After she proposed her study, they agreed to the plan. She returned a few months later, this time with a portable ultrasound machine to measure the size of the Bajau people’s spleens.


Dr. Melissa Ilardo taking an ultrasound scan of a Bajau diver’s spleen. Scientists have found that marine mammals with larger spleens can dive deeper — the enlarged spleen acts much like a bigger scuba tank. CreditPeter Damgaard

When people plunge into water, they respond with the so-called diving reflex: the heart rate slows and blood vessels constrict as a way to shunt blood to vital organs. The spleen also contracts, squirting a supply of oxygen-rich red blood cells into the circulation.

All mammals have a diving reflex, but marine mammals like seals have a particularly strong one. Scientists suspect that the reflex helps them dive deeper — as it turns out, seals with bigger spleens can dive deepest. An enlarged spleen seems to function like a bigger scuba tank.

Dr. Ilardo scanned the abdomens of the Bajau villagers and then traveled about 15 miles inland to a village occupied by farmers known as the Saluan. She scanned them, too.

When Dr. Ilardo compared scans from the two villages, she found a stark difference. The Bajau had spleens about 50 percent bigger on average than those of the Saluan.

Yet even such a remarkable difference might not be the result of evolution. Diving itself might somehow enlarge the spleen. There are plenty of examples of experience changing the body, from calloused feet to bulging biceps.

Only some Bajau are full-time divers. Others, such as teachers and shopkeepers, have never dived. But they, too, had large spleens, Dr. Ilardo found. It was likely the Bajau are born that way, thanks to their genes.


Bajau homes built on stilts. Only some Bajau are full-time divers, while others are teachers and shopkeepers, but Dr. Ilardo found that all Bajau had enlarged spleens. CreditMelissa Ilardo

On her visit to Sulawesi, Dr. Ilardo also took mouth swabs from the Bajau and Saluan from which she extracted DNA. She looked at the genetic variations in each village and compared them to people from neighboring countries, such as New Guinea and China.

A number of genetic variants have become unusually common in the Bajau, she found. The only plausible way for this to happen is natural selection: the Bajau with those variants had more descendants than those who lacked them.

One variant of a gene called PDE10A influenced the size of spleens in the Bajau. People with one copy of the mutant gene had bigger spleens than those with none. People with two copies had even bigger spleens.

Scientists had never found a special role for PDE10A in the spleen. “This connection was a bit bizarre,” Dr. Ilardo said.

But there’s one possible link. PDE10A has been shown to control the level of thyroid hormone in the body. And scientists have found that injecting thyroid into mice with stunted spleens can make the organs grow larger.

Still, that wouldn’t pin down exactly how PDE10A became so common in the Bajau. “It’s the question that’s harder than others,” said Rasmus Nielsen, a geneticist at the University of California, Berkeley, who collaborated with Dr. Ilardo.


A diver with a traditional wooden mask. Some researchers suspect the Bajau only began diving when Chinese demand for sea cucumbers rose in the 1600s. Other experts believe the Bajau began earlier, at the end of the last Ice Age, when rising sea levels turned the region into islands. CreditMelissa Ilardo

For her own part, Dr. Ilardo suspects that natural selection favored the Bajau variant of PDE10A because deep diving is so risky. “I would think, as morbid as it is, that if they didn’t have this, it would kill them,” she said.

François-Xavier Ricaut, an anthropologist at the University of Toulouse who was not involved in the study, said that it wasn’t clear yet how quickly this evolutionary change happened.

Some researchers suspect the Bajau only began diving to great depths when a market for sea cucumbers opened up in China in the 1600s. Or perhaps the adaptation began thousands of years earlier, at the end of the Ice Age, when rising sea levels turned the region around Indonesia into islands.

“This study acts as a cornerstone for exciting questions to follow,” said Dr. Ricaut.

Dr. Ilardo said there were likely a number of other genes that help the Bajau dive. She and her colleagues also found evidence for natural selection on a gene called BDKRB2.

In a study published last year, Russian scientists discovered that it plays a role in the diving reflex. In people with variants of BDKRB2, blood vessels are more tightly constricted when they plunge their faces into cold water.

To see if that’s the case with the Bajau, Dr. Ilardo will need to take another trip to beautiful Sulawesi. “I would be happy doing this as long as I can,” she said.


This article was originally published in The New York Times.  Read the original article.

A group of people with an amphibious life have evolved traits to match

THE Bajau, a people of the Malay Archipelago, spend almost all of their lives at sea. They live either on boats or in huts perched on stilts on shallow reefs, and they migrate from place to place in flotillas that carry entire clans. They survive on a diet composed almost entirely of seafood. And to gather this they spend 60% of their working day underwater.

Unsurprisingly, their diving abilities are prodigious. They sometimes descend more than 70 metres, and can stay submerged for up to five minutes, using nothing more than a set of weights to reduce buoyancy and a pair of wooden goggles fitted with lenses fashioned from scrap glass that are resistant to distortion by the pressure at such depth. Since the Bajau have lived like this for a long time (historical evidence suggests at least 1,000 years), many researchers have speculated that they carry genetic traits which adapt them to their remarkable lifestyle. Now, as they report in Cell, Melissa Ilardo and Rasmus Nielsen of the University of California, Berkeley have shown that this is so.

Immersing someone’s face in cold water and thus requiring him to hold his breath triggers what is known as the diving response. This involves a lowering of the heart rate to conserve oxygen; the redirection of blood from surface tissues to the most oxygen-sensitive organs, such as the brain, the heart and the lungs; and contraction of the spleen, an organ that acts as an emergency reserve of oxygenated red blood cells, so that an increased supply of these cells is released into the bloodstream. Ms Ilardo and Dr Nielsen decided to investigate whether the genetics and anatomy of the Bajau promote these responses.

To do so, Ms Ilardo travelled to Indonesia and recruited 59 Bajau who were willing to give her samples of saliva for DNA analysis and also to have their spleens measured ultrasonically. To act as controls, she also recruited 34 members of the Saluan, a group of landlubbing but closely related neighbours of the Bajau. The spleen scans showed that the Bajau’s are 50% larger than those of the Saluan—a difference unconnected with whether an individual was a prolific diver or one who spent most of his time working above the waves on a boat. This suggests that it is Bajau lineage, rather than the actual activity of diving, which is responsible for a larger spleen.

DNA analysis told a similar story. One intriguing result was a mutation in part of the Bajau genome that regulates the activity of a gene known to be involved in controlling blood flow, such that blood can be sent preferentially to oxygen-hungry vital organs. Another was a mutation in a gene responsible for the production of carbonic anhydrase, an enzyme that slows the build up of carbon dioxide in the bloodstream, a phenomenon that is associated with extreme diving. Changes in genes associated with muscle contractions around the spleen and with responses to low oxygen levels also turned up.

Putting these results together, Ms Ilardo and Dr Nielsen argue that the need to collect food by diving has indeed led to the evolution, in the case of the Bajau, of a group who are literally born to dive. Whether that evolution was driven by the failure of those who could not dive well to collect enough food to sustain a large family, or rather, of their dying in the attempt to do so, remains to be determined.




This article was originally published in The Economist. Read the original article.

What’s Behind Many Mystery Ailments? Genetic Mutations, Study Finds

Gregor Mendel discovered fundamental rules of genetics by raising pea plants. He realized that hidden factors — we now know them to be genes — were passed down from parents to offspring.

It wasn’t until the early 1900s, long after Mendel’s death, that doctors discovered that humans weren’t so very different. Some diseases, it turns out, are inherited — they’re Mendelian.

Today, scientists have identified over 7,000 Mendelian diseases, and many are discovered with screenings of children and adults. But a new study suggests that many disorders go undetected.

With a database of electronic health records and DNA samples, a team of scientists has found that 3.7 percent of patients in a hospital system carried a genetic variant linked to a disease. It’s possible that as many as 4.5 percent of cases of apparently nongenetic diseases, from infertility to kidney failure, are the result of such mutations.

The study also suggests that it may be possible to catch more of these hidden disorders with a computer program that flags suspicious clusters of symptoms in groups of patients. That would be an enormous step forward for patients coping with unexplained ailments.

The study, published Thursday in Science, represents the first large-scale search of electronic health records for hidden Mendelian diseases. But Dr. Joshua C. Denny, a biomedical informatics researcher at the Vanderbilt University School of Medicine and co-author of the new study, suspected that it only revealed the tip of a genetic iceberg. Much larger databases including DNA and records for hundreds of thousands of people are being built, and searching them may uncover many more hidden mutations.

“I’m sure there’s a whole bunch else out there that we will discover,” Dr. Denny said.

He and his colleagues gathered data from Vanderbilt’s massive electronic health records system, which includes more than two million patients. More than 225,000 have signed up as volunteers for genetic research, allowing scientists to analyze their DNA.

The researchers picked out 21,701 patients from the database and surveyed all the symptoms recorded for each one. They then compared the symptoms to those seen in 1,204 Mendelian diseases.

It was a difficult task. These disorders can produce a number of symptoms, and each patient may have a different combination of them.

And some symptoms linked to a Mendelian disease may also be signs of other diseases. Cystic fibrosis can cause asthma and recurrent infections, for instance — but those symptoms alone aren’t enough to diagnose the disease.

Dr. Denny and his colleagues developed a scoring system to determine how likely it was that each patient in their study suffered each Mendelian disease. If a patient had a rare symptom linked to a disease, she scored a lot of points. A common symptom earned her far fewer points.

The researchers identified groups of people with symptoms strongly suggesting they shared a Mendelian disease. The researchers went on to examine the DNA of these patients to see if they also shared a mutation.

Dr. Denny would have been happy just to find a few undiagnosed patients. Instead, the team found 807 patients carrying mutations in genes linked to 17 different diseases, such as cystic fibrosis or hemochromatosis, a disorder that causes iron to build up in the blood.


Gregor Mendel, a monk in what is now the Czech Republic, discovered basic principles of heredity by observing plants in his garden.

Only eight of these patients had gotten a test that revealed the mutation. In other cases, doctors had tested for the wrong disease and gotten a negative result. Many times, the doctors hadn’t ordered any genetic tests at all.

Typically, these disorders can be passed down in one of two ways. A dominant disease, like Huntington’s, requires inheriting just one defective copy of a gene from a parent. Recessive diseases, such as sickle cell anemia, usually require two defective copies of the same gene.

The mutations that the scientists discovered often didn’t fit the standard profile for the diseases. Many of the patients had conditions that are considered recessive, yet they carried a just single defective copy of the gene.

A single defective copy may cause milder versions of Mendelian diseases, Dr. Denny suspects.

The researchers identified 36 people, for example, who carried only one defective version of a gene called AGXT. Two copies of the gene cause a disease known as primary hyperoxaluria, which can result in kidney failure in toddlers. The patients identified in the new study also suffered kidney problems — but not in the first few years of life.

One patient who turned up in their search had kidney stones at age 15. That’s unusual — but apparently not enough to lead the patient’s doctors to suspect primary hyperoxaluria.

“It’s not as simple as what we learned in high school genetics,” Dr. Denny said.

These results are all the more surprising given how modest Dr. Denny’s search was. He only looked for a limited number of mutations in a relatively small group of people, all of whom were of European descent. (Much of what is known about gene variants that cause disease was discovered by researching predominantly white populations.)

“I’m kind of surprised we found anything. The fact that we did means there’s maybe a lot out there that we don’t know,” Dr. Denny said.

Heidi L. Rehm, a molecular geneticist at Brigham and Women’s Hospital who was not involved in the study, said many doctors do not suspect that their patients are suffering from a Mendelian disorder unless they suffer severe textbook symptoms.

“They simply never order any genetic testing, and then you never develop an understanding that it’s genetic to begin with,” she said.

Overlooking the genetic causes of diseases can seriously harm patients. “There are people here who had kidney and liver transplants that could potentially have been avoided,” Dr. Denny said.

Undiagnosed hemochromatosis, for example, can lead to liver failure. Of the 40 people Dr. Denny and his colleagues identified with hemochromatosis, four needed liver transplants.

Yet hemochromatosis can be readily treated by having patients donate blood on a regular basis, which helps rid them of excess iron.

The strategy employed by the research team was startlingly effective at identifying potential causes of disease. In the long run, Dr. Denny and Dr. Rehm agreed, the best solution might be to sequence the entire genome of every patient — in childhood, or even at birth.

But such a policy would create an unmanageable glut of genetic data.

“I don’t think we’re ready to do that,” Dr. Denny said.

This article was originally published in The New York Times.  Read the original article.

Can You Get Two Colds at Once?

Q. Can I get two colds at once?

A. Yes, you can. The phenomenon is known medically as coinfection and occurs when two germs, in this case viruses, cause infections at the same time.

More than 100 viruses can cause the common cold, so it’s not unusual to be exposed to two at once. And, since one virus doesn’t typically confer immunity against the other, it’s not unusual to be infected by two viruses at once.

The best data about coinfection come from studies of more serious viruses, such as H.I.V. and hepatitis. These studies show that coinfection can worsen, ameliorate or have no impact on the course of an illness. The outcome depends on the viruses involved.

With H.I.V., coinfection with the two main types, H.I.V.-1 and H.I.V.-2, is actually beneficial. It slows the progression of the disease. Coinfection with H.I.V. and hepatitis C virus, on the other hand, worsens the outcome.

With influenza viruses, which cause respiratory infections similar to that of the common cold, coinfection is uncommon. Coinfection with influenza A and B, two major types of flu virus, occurs in fewer than 2 percent of cases but doesn’t seem to affect the overall outcome.

Coinfection with the common cold has proved difficult to study in the past because of the large number of viruses that can cause a cold. In the last few years, however, advances in molecular genetics have afforded scientists insights into the rhinovirus, the most common cause of the common cold.

In 2009, scientists were able to sequence all of the genetic material from the 99 known strains of rhinovirus. They found that coinfection with multiple strains is a common occurrence. They also found that coinfection provided viruses an opportunity to mutate into new strains.

Diagnostic tests for many of the viruses that cause colds have now become commercially available. In 2013, doctors used these tests to study 225 children in day care. Almost half were infected with more than one virus when they got sick. Children infected with multiple viruses did not appear to be sicker than those infected with a single virus, but they stayed sick longer. These findings were recently confirmed by a systematic review of all published studies.

So while you can get two colds at once, you probably won’t feel any worse than you would with one. The difference that you might experience is being sick for longer than you might otherwise expect.

This article was originally published in The New York Times.  Read the original article.

How Exercise Can Keep Aging Muscles and Immune Systems ‘Young’

Remaining physically active as we grow older could help to keep our muscles and immune systems robust, according to two inspiring new studies of older recreational cyclists.

Together, the experiments add to growing evidence that some of our assumptions about aging may be outdated and we might have more control over the process than we think.

Aging often seems inexorable and unvarying, and, in chronological terms, it is. The years mount at the same pace for each of us.

But our bodies’ responses to the passage of time can differ. While most people become frail, a few remain spry.

These differences recently prompted a group of British scientists to wonder whether our beliefs about what is normal and inevitable with physical aging might be limited or incorrect, and in particular, whether we might be ignoring the role of exercise.

Exercise among middle-aged and older adults in the Western world is rare. By most estimates, only about 10 percent of people past the age of 65 work out regularly.

So, our expectations about what is normal during aging are based on how growing older affects sedentary people.

But the British scientists, many of them recreational athletes, suspected that exercise might have an impact on the trajectory of physical aging and, if so, alter our beliefs about what “normal” aging means.

To test that possibility, they decided to seek out a group of older men and women who had remained physically active as they aged and found them among local recreational cyclists. The dozens of male and female riders they eventually recruited were between the ages of 55 and 79, had been cycling for decades, and still pedaled about 400 miles per month. None were competitive athletes.

For their inaugural study of the riders, which was published in 2014, the scientists measured a broad range of the cyclists’ physical and cognitive abilities and compared them to those of sedentary older people and much younger men and women. The cyclists proved to have reflexes, memories, balance and metabolic profiles that more closely resembled those of 30-year-olds than of the sedentary older group.

That analysis had left many questions about exercise and physical activity unanswered, however. So for the two new studies, which were both published in Aging Cell this month, the researchers decided to refocus their inquiries and look closely at muscles and T cells, a key infection-fighting component of our immune system.

In most people, muscle health and immune response worsen after we arrive at middle age, with the effects accelerating decade by decade. But there had been hints in the first study’s data that the cyclists might be unusual in these regards.

So for one of the new studies, the researchers turned to muscle tissue that already had been biopsied from the legs of 90 of the riders. They wanted to compare various markers of muscle health and function across the riders’ age span. If the muscles of riders in their 70s resembled those of riders in their 50s, the scientists reasoned, then their physical activity most likely had altered and slowed the supposedly “normal” arc of muscular decline.

At the same time, other scientists delved into the riders’ immune systems, drawing blood from them, as well as from a group of sedentary older people and another of healthy young adults.

The two sets of scientists then dove into their data and both concluded that older cyclists are not like most of the rest of us. They are healthier. They are, biologically, younger.

Their muscles generally retained their size, fiber composition and other markers of good health across the decades, with those riders who covered the most mileage each month displaying the healthiest muscles, whatever their age.

The impacts on riders’ immune system also were marked. In the older sedentary people, the output of new T cells from the thymus glands was low. The inactive older peoples’ thymus glands also were atrophied, compared to those of the younger group.

The aging cyclists, on the other hand, had almost as many new T cells in their blood as did the young people. Those who exercised also showed high levels of other immune cells that help to prevent autoimmune reactions and of a hormone that protects the thymus against shrinkage.

The researchers theorize that the results of the two studies are interrelated. Muscles are one of the sources of the hormone that protects the thymus.

“So more muscle means more of that hormone,” says Janet Lord, the director of the Institute of Inflammation and Aging at the University of Birmingham, who was a co-author of both studies.

The older cyclists’ immune systems were not impervious to aging, of course. Many of their existing T cells showed signs of senescence, which means that they had grown feeble and were unlikely to fight infections well anymore.

The results also are limited to recreational British cyclists. They cannot tell us if other types and amounts of physical activity would necessarily have the same effects or whether someone could begin exercising at, say, age 60 and expect to benefit to the same extent as someone who has exercised lifelong.

But even with those caveats, Dr. Lord says, “the message of these studies is that much of what we previously thought of as inevitable in aging is in fact preventable.”

This article was originally published in The New York Times.  Read the original article.

Pioneering Alzheimer’s study in Colombia zeroes in on enigmatic protein

Jhon Kennedy was building a house for his family when he realized that his 45-year-old father was beginning to struggle with daily life. His dad tried to help with the construction project but often forgot to complete simple tasks. And he kept getting lost on the way home from work.

Jhon Kennedy wasn’t surprised: his four uncles had also started to lose their memories, one by one. But their doctors in Colombia’s rural Antioquia region, which is known for its mountainous terrain and coffee plantations, had never heard of early-onset dementia. It wasn’t until a cousin learned about a study of Alzheimer’s disease at the University of Antioquia in Medellín that Jhon Kennedy’s relatives understood the illness they faced. For more than three decades, researchers there have been tracking a genetic mutation — common in the region — that causes Alzheimer’s to strike people in their 40s and 50s.

Later this year, a team at the university will begin scanning the brains of some Alzheimer’s-study participants with a technique that is available only in a few major medical centres worldwide. It will allow the researchers to track a protein called tau, which accumulates rapidly in the brains of people with the disease as symptoms begin to emerge. Watching tau form in real time could reveal the role it plays in Alzheimer’s, says Francisco Lopera, the neurologist who is leading the research.

Many scientists have long believed that the disease is triggered by another protein, amyloid, that builds up in the brains of people with Alzheimer’s. But several drugs that reduce amyloid levels have failed to relieve the symptoms of the disease in clinical trials, increasing researchers’ interest in the role of tau.

If all goes well, Lopera’s team will soon be the first in Colombia with the ability to scan people’s brains for tau. The team has already conducted a preliminary imaging study that yielded promising data. In February, he and his colleagues published the results of a pilot trial in which they brought 24 people from the same Colombian family to a facility in Boston, Massachusetts, and used positron-emission tomography (PET) to search their brains for tau. The researchers showed for the first time that tau begins to accumulate in the brains of people with the Antioquia mutation six years before they begin to show signs of disease1.

“This is a very definitive paper,” says Bruce Miller, a behavioural neurologist at the University of California, San Francisco. “I think it’s another piece of evidence that tau is very important and has a strong correlation with clinical symptoms.”

Genetic legacy

The genetic mutation that affected Jhon Kennedy’s father and uncles is famous in the field of Alzheimer’s research. It probably arrived in South America with Spanish conquerors 375 years ago, and now affects 25 extended families in Antioquia with more than 5,000 members. Researchers have published dozens of papers about this group, including some of the clearest proof that amyloid plaques can accumulate in the brain decades before symptoms of Alzheimer’s appear2.

But as questions have emerged about amyloid’s role in Alzheimer’s, researchers have taken a closer look at tau. The protein normally helps to stabilize the structures that allow neurons to communicate with one another. People with Alzheimer’s produce too much dysfunctional tau, causing these structures to collapse into tangles. The amount of the protein seems to increase at the same rate as a person’s symptoms.

In the past several years, researchers have developed radioactive biomarkers that allow them to detect tau in the brains of living people using PET. Studies using the technique have shown that tau accumulation in the brain’s language centres correlates with speech problems, for instance3. Several research groups are beginning clinical trials of drugs that scrub tau from the brain, although this work is at an early stage.

Jhon Kennedy and his 11 siblings each have a 50% chance of inheriting the Alzheimer’s mutation from their father. Eight have enrolled in Lopera’s trial and could be among the first people to have their brains scanned for tau in Colombia. None of the siblings in the study, including Jhon Kennedy, know if they carry the mutation.

Carlos Villegas and lab members at the NeuroBanc in Medellin

The brain lab at the University of Antioquia includes organs from 100 members of a single family who carried a genetic mutation for early-onset Alzheimer’s disease.Credit: Greg Kendall-Ball/Nature

Turning to tau

The study, which began in 2013, was designed to test whether crenezumab, a drug that clears amyloid plaques from the brain, could lessen symptoms of Alzheimer’s. Over the past five years Lopera’s team has recruited 252 participants who were between 30 and 60 years old. Those who carry the Alzheimer’s mutation will begin accumulating amyloid in their brains during their early 30s, on average.

Each participant in the trial will receive infusions of crenezumab or a placebo every other week, for five years. Lopera’s team is also testing their cognitive abilities, scanning their brains for amyloid and searching for blood proteins and other biomarkers that could be early indicators of disease.

The researchers hope to begin mapping the tau in participants’ brains in the coming months, once they receive final permission from regulators to produce the crucial radioactive marker, GPT1. When that happens, the team will join a handful of researchers worldwide that are using the technology. “It’s quite remarkable that a population that lives in such a remote area is getting access to some of the most advanced technology for understanding Alzheimer’s,” says Kenneth Kosik, a neuroscientist at the University of California, Santa Barbara.

Lopera and his colleagues want to determine how tau spreads through the brains of young people with Alzheimer’s, and whether that pattern mirrors the distribution of tau seen in elderly people with the disease. They hope to compare their results with data from two clinical trials of anti-amyloid drugs in the United States that have begun scanning participants’ brains for tau. Lopera, Kosik and other scientists are also beginning to identify families in Colombia with different genetic mutations that cause dementia or neurological disorders linked to tau, in the hope of imaging their brains too.

Lopera says that his team will not release any data from the crenezumab trial until it finishes in 2022. But if the results are promising, he adds, the researchers might give the drug to people younger than 30 who carry the mutation for early-onset Alzheimer’s. The scientists have identified nearly 500 young people who might be carriers, including Jhon Kennedy’s 15-year-old daughter. “She’s not worried about it,” Jhon Kennedy says. “She’s like me — she lives day by day.”



This article was originally published in Nature. Read the original article.

How Did Astronaut DNA Become ‘Fake News’?

“After year in space, astronaut Scott Kelly no longer has same DNA as identical twin,” the headline of a story on the Today show’s website, published Thursday, declared. Seven percent of his DNA, the story says, “has not returned to normal since he returned from space.”

Pretty amazing news, right? Too bad it’s not true.

This week, dozens of news organizations published stories with this or similar information. They cited a nasa study on the effects of space travel on the human body, with two subjects: astronauts Scott and Mark Kelly, identical twins. In 2015, Scott flew to the International Space Station and lived there for 340 days—a record for an American astronaut—while Mark stayed on Earth. Scientists examined the twins before, during, and after the mission.

While the study certainly detected some interesting changes in Scott after his return, space did not alter 7 percent of Scott’s DNA, the genetic code found in the cells in our bodies that makes us what we are.

Our cells have the same genes, which are made up of the same DNA, but genes behave differently; that’s how some cells produce hearts while others build lungs. The way genes are expressed can be affected by changes in the underlying sequence of DNA, by the random mutations we experience and collect over the course of our lives. But gene expression can also be influenced by all kinds of environmental factors, like stress and diet.

What the nasa study found was that some of Scott’s genes changed their expression while he was in space, and 7 percent of those genes didn’t return to their preflight states months after he came back. If 7 percent of Scott’s genetic code changed, as some of the stories suggested, he’d come back an entirely different species.

The misinterpretation of the study’s results spread like wildfire this week, across publications like CNN, USA Today, TimePeople, and HuffPost. Even Scott Kelly himself was fooled. “What? My DNA changed by 7 percent! Who knew? I just learned about it in this article,” he tweeted earlier this week, linking to a Newsweekarticle.“This could be good news! I no longer have to call @ShuttleCDRKelly my identical twin brother anymore.”

The stories reached a crescendo on Thursday. Geneticists who saw the news took to social media to groan about how wrong it was. The scientists behind the nasastudy, stunned by how quickly and fiercely the wrong news had taken off, were bombarded with calls and emails from reporters. They scrambled to set the record straight. “I never thought I’d find myself battling ‘fake news,’” says Christopher Mason, a geneticist at Weill Cornell Medicine in New York who led the study.  (He’ll be on NBC’s nightly news on Saturday trying to explain.)

A slew of new stories eventually appeared, this time debunking what had been reported. Google News highlighted a mix of inaccurate and accurate reports. By about 4 p.m., nasa released a statement to address the mayhem and confirm that Scott did not, in fact, come back from space a mutant.

“Mark and Scott Kelly are still identical twins,” nasa said. “Scott’s DNA did not fundamentally change. What researchers did observe are changes in gene expression, which is how your body reacts to your environment. This likely is within the range for humans under stress, such as mountain climbing or scubadiving.”

The whole thing was a mess. How exactly did this all happen?

First, about the study. It was actually the Kellys’ idea. Before Scott launched to the space station in 2014, the pair pointed out that since they’re identical twins, maybe the space agency could study what happens when one’s on the planet and the other isn’t. So nasa put a call out for proposals and then awarded the chosen researchers a combined $1.5 million over three years. When Scott returned in 2016, scientists spent months analyzing data, looking for evidence of genetic changes that potentially could be attributed to spaceflight.

The study has one big limitation: It’s a case study of a single participant, Scott. Mark is the only control group. If scientists detected changes in Scott’s gene activity, they would have no idea whether they were due to spaceflight or any number of other factors, some as simple as just being alive for a year.

For reasons that remain unclear, the news stories that erupted this week resurfaced a couple of nasa press releases from January, which came out after the study’s scientists presented some of their preliminary results at a conference. The releases were summaries, and some of the language was ripe for misinterpretation. “Another interesting finding concerned what some call the ‘space gene,’” one press release said. “Researchers now know that 93 percent of Scott’s genes returned to normal after landing. However, the remaining 7 percent point to possible longer-term changes in genes related to his immune system, DNA repair, bone-formation networks, hypoxia, and hypercapnia.”

First of all, there’s no such thing as a “space gene.” It’s just a term that some geneticists who are studying the astronauts use to refer to genes that maybe, someday, we can determine become expressed differently solely because of spaceflight.

The rest is pretty vague and potentially confusing if you’re not a geneticist. The study’s scientists haven’t released a formal, peer-reviewed paper about their findings, which is expected later this year, so this press release was all people had to go on. The press release should have referred to changes in the expression levelsof genes, and maybe tried explaining epigenetics—the study of modifications in gene behavior, and not in DNA itself. It could have even indicated that the finding wasn’t a shock.

“It’s not surprising that gene expression would change to adapt to a new environment,” says Chris Gunter, an associate professor at the Emory University School of Medicine in pediatrics and human genetics, who was not involved in the nasa study. “That’s one of the reasons that humans are absolutely amazing systems.”

Readers of the press release would have no idea whether a 7 percent change was even significant; after all, this is the first time we’ve studied gene expression in an astronaut. Nasa said the change was “very minimal” in its clarifying statement on Thursday. But by then, it was already too late.

Scott did experience some changes in his DNA. DNA is packaged into structures called chromosomes, which end in protective caps called telomeres. The study found that Scott’s telomeres lengthened while Scott was in space. This was a big surprise. On Earth, our telomeres shorten as we age, and the process can be accelerated by stress. Because spaceflight puts immense stressors on the human body, scientists had thought Scott’s telomeres would shrink.

“There was no doubt that there was telomere elongation in space, and they shortened dramatically when he came back,” says Susan Bailey, a radiation cytogeneticist and Colorado State University professor who led the telomere research. But “that is very separate from gene expression. It’s not the same thing at all.”

The media seems to have conflated this finding, the lengthening of the telomeres in Scott’s DNA, with the other—the changes in gene activity. Take, for example, the Newsweek story that Kelly tweeted. “Astronaut Scott Kelly’s DNA was altered by a year in space,” it says. True, if you’re talking about his telomeres. The next sentence, “Seven percent of his genes did not return to normal after he landed, researchers found.” Also true, if you’re talking about his gene expression. Unfortunately, when they’re combined like that, they’re misleading.

There was no evidence of the deliberate or malicious spread of misinformation in this saga. But the whole affair provides a fascinating case study in the concept of “fake news.” Last week, MIT released the results of a highly regarded, massive study on the spread of false information over a decade.  The research, which my colleague Robinson Meyer has described in detail, focused mostly on false and disparaging information in political news, but it has lessons for other realms as well.  The researchers found that fake news appeared to be more “novel” than real news. For example, tweets that spread false information used words associated with surprise and disgust, while tweets that shared accurate information used words associated with sadness and trust.

We saw this play out on Thursday. “After year in space, astronaut Scott Kelly no longer has same DNA as identical twin,” that Today headline proclaimed, highlighting the novel. “No, Scott Kelly’s year in space didn’t mutate his DNA,” a National Geographic headline replied, highlighting what was real.

This isn’t even the only time news about astronauts accidentally became “fake news.” In January, the Japanese astronaut Norishige Kanai tweeted that he had “somehow” grown nine centimeters after just a few months on the International Space Station. “I’ve really shot up, something I haven’t seen since high school,” he said it. The tweet spawned many excited news stories about the strange occurrence. Less than two days later, Kanai tweeted again to apologize. He had measured himself, and it turned out that he had only grown two centimeters, an unsurprising amount since zero gravity slightly stretches the spine. “This mismeasurement appears to have become a big deal, so I must apologize for this terrible fake news,” he said.

In November, the Russian cosmonaut Anton Shkaplerov gave an interview about an experiment that involved leaving microorganisms on the exterior of the International Space Station and periodically checking on them to see how they survived. “And now it turns out that somehow these swabs reveal bacteria that were absent during the launch of the ISS module,” he said. “That is, they have come from outer space and settled along the external surface.” News organizations took this and reported that—OMG—the Russians had discovered alien life sticking to the outside of the International Space Station. Others wrote stories debunking this—but not before the news had spread across the vastness of the internet.

As news coverage of Scott and his DNA reached a fever pitch Thursday, some wondered whether nasa should have waited to release results, even preliminary ones, from the study until after their paper came out, in order to reduce the risk of confusion. “It would have been better if we could have had the paper out sooner, but we’re just trying to be very careful about this,” Bailey says, about interpreting the results. “And this is a good example of why we’re being very careful. … We really do have some very definitive results coming out. Just wait for the paper.”

The release of preliminary results is also risky because scientists are far from making any definitive claims about how spaceflight affects human genes, as exciting as the investigation is. “What an incredible natural experiment to be able to study the effects of space on the human body. There’s a reason why twin studies are one foundational pillar of human genetics,” Gunter says. But, she adds, “we also need to acknowledge that we aren’t measuring ‘space versus Earth’—we are measuring a host of environmental components.”

The study’s investigators pretty much went in and measured everything they could find. In this kind of study, determining which factors led to which effects is nearly impossible. Nor can any results be extrapolated to astronauts or the general population. “The perfect nature-versus-nurture study would be many, many twins and many, many missions, and the challenge is we’ll probably never get that,” Mason says.

The twins study isn’t perfect, but it’s certainly a start. “One of the things I’m seeing on Twitter is that it’s an n=1 experiment, but this is kind of the reality of it,” says John Greally, the director of the Center for Epigenomics at Albert Einstein College of Medicine. “We can only do experiments on very small numbers of space travelers.”

And it’s certainly better to use twins. “If you took yourself and myself and we didn’t go to space, and you took exactly the same cells from the two of us, there would be big differences in things like DNA methylation and gene expression, which are due to our being genetically different,” Greally says. “[Mason] has been able to get rid of that one problem by using the identical Kelly twins.”

By Friday morning, most of the news stories about Scott Kelly’s DNA had been updated, their headlines tweaked and claims corrected. The storm has passed. But for a brief moment in time, many people out there, including Scott himself, believed that an American astronaut returned from a year in space with his genetic code completely transformed. It was, technically, fake news. But it was an honest mistake, not a devious campaign of misinformation.

“The way that people have run with this and overinterpreted is human nature. You don’t need to talk to a genomics person to get feedback on that,” Greally says. “But I love the fact that people care. It would be so much worse if they didn’t.”

This article was originally published in The Atlantic. Read the original article.