How Gut Bacteria Are Shaking Up Cancer Research

 http://www.bloomberg.com/

Makiko Kitamura 

• Roche says it plans to study role of microbiome in cancer
• Vedanta expects more drug companies to enter the field

Top scientists at Roche Holding AG and AstraZeneca Plc are sizing up potential allies in the fight against cancer: the trillions of bacteria that live in the human body.
"Five years ago, if you had asked me about bacteria in your gut playing an important role in your systemic immune response, I probably would have laughed it off," Daniel Chen, head of cancer immunotherapy research at Roche’s Genentech division, said in a phone interview. "Most of us immunologists now believe that there really is an important interaction there."
Two recent studies published in the journal Science have intrigued Chen and others who are developing medicines called immunotherapies that stimulate the body’s ability to fight tumors.
In November, University of Chicago researchers wrote that giving mice Bifidobacterium, which normally resides in the gastrointestinal tract, was as effective as an immunotherapy in controlling the growth of skin cancer. Combining the two practically eliminated tumor growth. In the second study, scientists in France found that some bacterial species activated a response to immunotherapy, which didn’t occur without the microbes.

Human Microbiome

That’s increased drugmakers’ interest in the human microbiome -- the universe of roughly 100 trillion good and bad bacteria, fungi and viruses that live on and inside the body. Roche is already undertaking basic research in the field and plans to investigate the microbiome’s potential for cancer treatment, Chen said.
"Certainly, we are already scanning the space for interesting opportunities as the science continues to emerge," he said. "We are very interested in testing these in a controlled setting."
Some experienced investors are skeptical and see the possibility of an approved product for cancer to be at least five years away.
"To therapeutically influence the microbiome long-term in humans is a big hurdle," said Sander van Deventer, managing partner at venture-capital firm Forbion Capital Partners. "The microbiome is very stubborn. Everything we’ve done so far has only had a temporary effect."

Nestle’s Investment

Earlier in his career, van Deventer chaired the department of gastroenterology and hepatology at the Academic Medical Center in Amsterdam, the first clinic in the world to perform fecal transplants to fight hospital infection Clostridium difficile with good bacteria. Forbion hasn’t yet invested in any microbiome biotechs, "but we’re looking at all of them all the time," he said.
Efforts are under way to turn bacteria into regulated pharmaceutical products to treat illnesses of the gut, where the microbes reside.
Nestle SA last January invested $65 million in ambridge, Massachusetts-based Seres Therapeutics Inc., which is developing a treatment for Clostridium difficile, which affects the digestive system. That follows early efforts to harness the microbiome’s benefits, which spawned probiotic foods and supplements as well as transplants of healthy bacteria.
The promise in cancer will draw more large drugmakers into exploring the human microbiome, said Bernat Olle, chief executive officer of Vedanta Biosciences, a Boston-based startup.

Treatment Potential

"That’s the sense we get based on how we’re being approached by new pharma groups and how serious they seem to be about wanting to enter the field,” Olle said in a phone interview. Vedanta last year announced a license agreement with Johnson & Johnson on its experimental microbiome drug for inflammatory bowel disease.
Another startup, 4D Pharma Plc, in November said it had discovered a bacterium that produces a response comparable to that of an immunotherapy in animal tests for breast and lung cancers. The London-listed company plans to start trials in patients by the end of this year. To support research in autoimmune and neurological diseases, in addition to cancer, the company has raised over 100 million pounds ($140 million) from investors over the last two years, CEO Duncan Peyton said in a phone interview.
French biotech Enterome is taking a different approach: developing treatments based on bacterial secretions. Enterome plans to close a private financing round of about 15 million euros this month, according to CEO Pierre Belichard. More news may be on the way.

‘Active Discussions’

"We are in active discussions with the usual suspects in the immunotherapy space," Belichard said in an interview in London.
Those active in the field include a wide range of pharma companies including AstraZeneca, Roche, Bristol-Myers Squibb Co., and Merck & Co.
"Personally, I think it’s a fascinating area," Susan Galbraith, head of oncology research at AstraZeneca, said in an interview in London.
Studies have shown that immunotherapies have varying degrees of success even in genetically identical mice, and the Science study from Chicago suggests that the diversity of the microbiome may help explain that variability, Galbraith said. AstraZeneca isn’t conducting its own research in the area and would prefer to wait to see evidence in human trials before getting involved, she said.
The sheer number of bacteria, some of which could actually switch off an immune response, and the question of how much bacteria is needed, make it a complex area of research, Roche’s Chen said. It’s possible that the same bacteria could induce both harmful and helpful responses, depending on the patient, he said.
Still, "it’s one of the most interesting developments we’ve seen in science over the last several years," he said.

Oldest ever human genome sequence may rewrite human history

Daily news

14 March 2016

https://www.newscientist.com/

What secrets lurk in the pit of bones?

Javier Trueba, Madrid Scientific Films

The oldest ever human nuclear DNA to be reconstructed and sequenced reveals Neanderthals in the making – and the need for a possible rewrite of our own origins.
The 430,000-year-old DNA comes from mysterious early human fossils found in Spain’s Sima de los Huesos, or “pit of bones”.
The fossils look like they come from ancestors of the Neanderthals, which evolved some 100,000 years later. But a 2013 study found that their mitochondrial DNA is more similar to that of Denisovans (see video, below), who also lived later and thousands of kilometres away, in southern Siberia.
So who were the Sima people – and how are they related to us?

To find out, a team led by Matthias Meyer at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, pieced together parts of the hominin’s nuclear DNA from samples taken from a tooth and a thigh bone.

One of the Sima de los Huesos skeletons

Javier Trueba, Madrid Scientific Films

The results suggest they are more closely related to ancestors of Neanderthals than those of Denisovans – meaning the two groups must have diverged by 430,000 years ago. This is much earlier than the geneticists had expected.
It also alters our own timeline. We know that Denisovans and Neanderthals shared a common ancestor that had split from our modern human lineage. In light of the new nuclear DNA evidence, Meyer’s team suggests this split might have happened as early as 765,000 years ago.
Previous DNA studies had dated this split to just 315,000 to 540,000 years ago, says Katerina Harvati-Papatheodorou at the University of Tubingen in Germany.
But a date of 765,000 years ago actually brings the DNA evidence more in line with some recent fossil interpretations that also suggest an older divergence between modern humans and the ancestor of the Neanderthals and Denisovans.
“I am very happy to see that ideas about the divergence based on ancient DNA and on anatomical studies of the fossil record seem to be converging,” says Aida Gómez-Robles at George Washington University in Washington DC, who was involved in the fossil research.

Tree redrawn?

But if such an ancient split is correct, we might have to redraw parts of our evolutionary tree.
Conventional thinking is that modern humans, Neanderthals and Denisovans all evolved from an ancient hominin called Homo heidelbergensis.
However, H. heidelbergensis didn’t evolve until 700,000 years ago – potentially 65,000 years after the split between modern humans and the Neanderthals and Denisovans.
Instead, another, obscure species called Homo antecessor might now be in the frame as our common ancestor.
This species first appeared more than a million years ago – and its face is very similar to that of modern humans, says Chris Stringer at the Natural History Museum in London.

Further puzzles

“Research must now refocus on fossils from 400,000 to 800,000 years ago to determine which ones might actually lie on the respective ancestral lineages of Neanderthals, Denisovans and modern humans,” he says.
Another puzzle remains. The study confirmed a previous finding that the mitochondrial DNA of the Sima hominin is more similar to Denisovans than to Neanderthals – but no one knows why.
Perhaps there was another unidentified lineage of hominins in Eurasia that interbred with the ancestors of both – but not with the particular group of hominins that evolved into the Neanderthals.
Or, Meyer says, perhaps such mitochondrial DNA was typical of early Neanderthals and Denisovans, and it was only later that Neanderthals acquired different mitochondrial DNA from an African population of “proto-Homo sapiens“.
Journal reference: Nature, DOI: 10.1038/nature17405
Find out more about the oldest human genome dug up in Spain’s pit of bones:

 

Neanderthal diet: Only 20 percent vegetarian

Researchers have long debated the precise diet of early humans, but the latest study is the first to nail down precise percentages.

By Brooks Hays   |   March 14, 2016 at 12:33 PM

Fossil analysis suggests Neanderthals ate a diet of
80 percent meat. Photo by OrdinaryJoe/Shutterstock

TUBINGEN, Germany, March 14 (UPI) -- Neanderthals were apparently too busy hunting and scavenging to pay much attention to Michael Pollan's dietary advice: eat mostly plants.
New isotopic analysis suggests prehistoric humans ate mostly meat. As detailed in a new study published in the journal Quaternary International, the Neanderthal diet consisted of 80 percent meat, 20 percent vegetables.
Researchers in Germany measured isotope concentrations of collagen in Neanderthal fossils and compared them to the isotopic signatures of animal bones found nearby. In doing so, scientists were able to compare and contrast the diets of early humans and their mammalian neighbors, including mammoths, horses, reindeer, bison, hyenas, bears, lions and others.
"Previously, it was assumed that the Neanderthals utilized the same food sources as their animal neighbors," lead researcher Herve Bocherens, a professor at the University of Tubingen's Senckenberg Center for Human Evolution and Palaeoenvironment, said in a news release.
"However, our results show that all predators occupy a very specific niche, preferring smaller prey as a rule, such as reindeer, wild horses or steppe bison, while the Neanderthals primarily specialized on the large plant-eaters such as mammoths and woolly rhinoceroses," Bocherens explained.
All of the Neanderthal and animal bones, dated between 45,000 and 40,000 years old, were collected from two excavation sites in Belgium.
Researchers have long debated the precise diet of early humans, but the latest study is the first to nail down precise percentages.
Bocherens and his colleagues are hopeful their research will shed light on the Neanderthals' extinction some 40,000 years ago.
"We are accumulating more and more evidence that diet was not a decisive factor in why the Neanderthals had to make room for modern humans," he said.

Humans Interbred With Hominins on Multiple Occasions, Study Finds

Carl Zimmer

MATTER MARCH 17, 2016

Continue reading the main story Share This Page

Photo

Skulls of the Neanderthal man. Credit European Pressphoto Agency

The ancestors of modern humans interbred with Neanderthals and another extinct line of humans known as the Denisovans at least four times in the course of prehistory, according to an analysis of global genomes published on Thursday in the journal Science.

The interbreeding may have given modern humans genes that bolstered immunity to pathogens, the authors concluded.

“This is yet another genetic nail in the coffin of our over-simplistic models of human evolution,” said Carles Lalueza-Fox, a research scientist at the Institute of Evolutionary Biology in Barcelona who was not involved in the study.

The new study expands on a series of findings in recent years showing that the ancestors of modern humans once shared the planet with a surprising number of near relatives — lineages like the Neanderthals and Denisovans that became extinct tens of thousands of years ago.

Before disappearing, however, they interbred with our forebears on at least several occasions, and today we carry DNA from these encounters.

The first clues to ancient interbreeding surfaced in 2010, when scientists discovered that some modern humans — mostly Europeans — carry DNA that matches material recovered from Neanderthal fossils.

Later studies showed that the forebears of modern humans first encountered Neanderthals after expanding out of Africa more than 50,000 years ago.

But the Neanderthals were not the only extinct humans that our own ancestors found. A finger bone discovered in a Siberian cave, called Denisova, yielded DNA from yet another group of humans.

Research later indicated that all three groups — modern humans, Neanderthals and Denisovans — shared a common ancestor who lived roughly 600,000 years ago. And, perhaps no surprise, some ancestors of modern humans also interbred with Denisovans.

Some of their DNA has survived in people in Melanesia, a region of the Pacific that includes New Guinea and the islands around it.

Those initial discoveries left major questions unanswered, such as how often our ancestors interbred with Neanderthals and Denisovans. Scientists have developed new ways to study the DNA of living people to tackle these mysteries.

Joshua M. Akey, a geneticist at the University of Washington, and his colleagues analyzed a database of 1,488 genomes from people around the world. The scientists added 35 genomes from people in New Britain and other Melanesian islands in an effort to learn more about Denisovans in particular.

The researchers found that all the non-Africans in their study had Neanderthal DNA, while the Africans had very little or none. That finding supported previous studies.

But when Dr. Akey and his colleagues compared DNA from modern Europeans, East Asians and Melanesians, they found that each population carried its own distinctive mix of Neanderthal genes.

The best explanation for these patterns, the scientists concluded, was that the ancestors of modern humans acquired Neanderthal DNA on three occasions.

The first encounter happened when the common ancestor of all non-Africans interbred with Neanderthals.

The second occurred among the ancestors of East Asians and Europeans, after the ancestors of Melanesians split off. Later, the ancestors of East Asians — but not Europeans — interbred a third time with Neanderthals.

Earlier studies had hinted at the possibility that the forebears of modern humans had multiple encounters with Neanderthals, but until now hard data was lacking.

“A lot of people have been arguing for that, but now they’re really providing the evidence for it,” said Rasmus Nielsen, a geneticist at the University of California, Berkeley, who was not involved in the new study.

Scientists create chickens with dinosaur legs, because why not

By Lulu Chang 2 hours ago

Oh how the mighty dinosaurs have fallen. It’s a bit sad that the descendants of the magnificent creatures who once ruled the Earth have stubby wings and are the most commonly consumed meat in America (yes, I’m talking about the chicken). Such is the circle of life. And now, in an attempt to restore a bit of the glory of dinosaurs (or just create a truly bizarre looking animal), scientists have genetically modified chickens to give them dinosaur legs. Because science.
Interestingly enough, because of the close genetic relationship the modern day chicken shares with the prehistoric giant, the researchers involved with the wacky task simply had to silence a gene that chickens typically express. No gene insertion or further manipulation — just a (highly complex) flip of a switch.
The precise gene suppressed by the Chilean scientists, headed by Joâo Botelho
At Universidad de Chile is one called the Indian Hedgehog. This gene is crucial to the development of chicken’s bones, and when turned off, apparently allows the birds to develop a bone structure that looks just like the lower leg of a raptor. Chicken on top, dinosaur on the bottom.
Related: Just For the Tech of It: Martian crops and dinosaur chickens
This is by no means the first time that Botelho or other scientists have engineered a bird to go back to its more magnificent origins. Botelho also managed to undo the backward-facing perching toe common in birds to produce a front-facing toe — much like what dinosaurs had. And at Yale, a chicken was given a dinosaur-esque snout when its gene expression was altered at the embryo stage.
This sort of work is taking place across the country, and indeed, across the world, says Jack Horner, a famous paleontologist whose expertise was consulted in each and every one of the Jurassic Park films. At his lab at Montana State University, scientists are working to “ genetically alter a chicken egg to produce a more prehistoric version of the animal, complete with velociraptor-shaped head, arms, clawed hands and long tail,” the Post Register reports. But don’t worry, researchers say that we won’t be plunged into a real life version of the movies anytime soon.
“The experiments are focused on single traits, to test specific hypotheses,” says Alexander Vargas, who heds the lab in which Botelho works. “Not only do we know a great deal about bird development, but also about the dinosaur-bird transition, which is well-documented by the fossil record. This leads naturally to hypotheses on the evolution of development, that can be explored in the lab.”
Just call it scientific curiosity, and enjoy the strange but wonderful results that have come out of it … thus far.

Also watch: Raimond de Hullu’s vision for Oas1s green buildings

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Oh how the mighty dinosaurs have fallen. It’s a bit sad that the descendants of the magnificent creatures who once ruled the Earth have stubby wings and are the most commonly consumed meat in America (yes, I’m talking about the chicken). Such is the circle of life. And now, in an attempt to restore a bit of the glory of dinosaurs (or just create a truly bizarre looking animal), scientists have genetically modified chickens to give them dinosaur legs. Because science.
Interestingly enough, because of the close genetic relationship the modern day chicken shares with the prehistoric giant, the researchers involved with the wacky task simply had to silence a gene that chickens typically express. No gene insertion or further manipulation — just a (highly complex) flip of a switch.
The precise gene suppressed by the Chilean scientists, headed by Joâo Botelho
At Universidad de Chile is one called the Indian Hedgehog. This gene is crucial to the development of chicken’s bones, and when turned off, apparently allows the birds to develop a bone structure that looks just like the lower leg of a raptor. Chicken on top, dinosaur on the bottom.
Related: Just For the Tech of It: Martian crops and dinosaur chickens
This is by no means the first time that Botelho or other scientists have engineered a bird to go back to its more magnificent origins. Botelho also managed to undo the backward-facing perching toe common in birds to produce a front-facing toe — much like what dinosaurs had. And at Yale, a chicken was given a dinosaur-esque snout when its gene expression was altered at the embryo stage.
This sort of work is taking place across the country, and indeed, across the world, says Jack Horner, a famous paleontologist whose expertise was consulted in each and every one of the Jurassic Park films. At his lab at Montana State University, scientists are working to “ genetically alter a chicken egg to produce a more prehistoric version of the animal, complete with velociraptor-shaped head, arms, clawed hands and long tail,” the Post Register reports. But don’t worry, researchers say that we won’t be plunged into a real life version of the movies anytime soon.
“The experiments are focused on single traits, to test specific hypotheses,” says Alexander Vargas, who heds the lab in which Botelho works. “Not only do we know a great deal about bird development, but also about the dinosaur-bird transition, which is well-documented by the fossil record. This leads naturally to hypotheses on the evolution of development, that can be explored in the lab.”

Just call it scientific curiosity, and enjoy the strange but wonderful results that have come out of it … thus far.

Dinosaur-era geckos and chameleons perfectly preserved in amber

https://www.newscientist.com/

Gloriously well preserved

Florida Museum of Natural History/Kristen Grace

They probably hid from feathered dinosaurs, only to end up stuck in redwood sap.
A new collection of 12 lizards preserved in amber dates back to middle of the Cretaceous period – when dinosaurs such as the massive Argentinosaurus were still around – and may include the ancestors of geckos and chameleons.
The specimens come from Myanmar’s Kachin state and are thought to have lived in tropical forest. Each is embedded in Burmese amber, which previous studies dated to about 100 million years old. Previously, we knew of only a few fragments of amber lizards from the time of the dinosaurs – when modern lizard groups first evolved, according to genetic analyses.
The lizards, discovered in private amber collections on loan to the American Museum of Natural History and Harvard University, are immaculate and unusually diverse. As such they suggest that major lizard groups were already established at that time. The specimens will now go on display at the Houston Museum of Natural Science.

“One of them is perhaps the best fossil gecko that is known in the world,” says Juan Daza of Sam Houston State University in Texas, whose team revealed the finds, and then used CT scans to study them (click on image below). It was so detailed the team initially thought it looked like a modern animal.

Florida Museum of Natural History/Kristen Grace

But it wasn’t recent. “We started looking at the characteristics we describe in modern species, and none of those match,” Daza says. The adhesive toe pads are already present in these ancient specimens, suggesting the gecko’s climbing lifestyle evolved much earlier than thought.
Another specimen has its tongue stuck out. With a narrow, extended tip, it matches no snake or lizard tongue ever found.
One small lizard is trapped next to a scorpion-like animal and a millipede. That proximity, plus the fact that modern lizards in tropical forests hunt arthropods, suggest these animals preyed on them, Daza says.
That particular lizard is doubly interesting. Its bone structure resembles that of a newborn chameleon, although it is about four times the age of the oldest chameleon-like fossils previously known.
It even has a weak jaw, which wouldn’t be good for biting prey – possible evidence that the modern chameleon’s method of grabbing prey with a projectile tongue is really an old adaptation, Daza says. The find may also challenge current view that chameleons originated in Africa.
The new specimens are beautiful and very exciting, says Michael Caldwell of the University of Alberta in Edmonton, Canada. “We really have had little to no previous fossil record detailing that part of the family tree of lizards,” he says.
But closer anatomical studies are now needed to determine where each lizard is best classified – especially the putative chameleon, he adds.

Read more: Stunning fossils: The seven most amazing ever found

Science Advances, DOI: 10.1126/sciadv.1501080