More than half your body is not human

More than half of your body is not human, say scientists.

Human cells make up only 43% of the body’s total cell count. The rest are microscopic colonists.

Understanding this hidden half of ourselves – our microbiome – is rapidly transforming understanding of diseases from allergy to Parkinson’s.

The field is even asking questions of what it means to be “human” and is leading to new innovative treatments as a result.

“They are essential to your health,” says Prof Ruth Ley, the director of the department of microbiome science at the Max Planck Institute, “your body isn’t just you”.

No matter how well you wash, nearly every nook and cranny of your body is covered in microscopic creatures.

This includes bacteria, viruses, fungi and archaea (organisms originally misclassified as bacteria). The greatest concentration of this microscopic life is in the dark murky depths of our oxygen-deprived bowels.

Prof Rob Knight, from University of California San Diego, told the BBC: “You’re more microbe than you are human.”

Originally it was thought our cells were outnumbered 10 to one.

“That’s been refined much closer to one-to-one, so the current estimate is you’re about 43% human if you’re counting up all the cells,” he says.

But genetically we’re even more outgunned.

The human genome – the full set of genetic instructions for a human being – is made up of 20,000 instructions called genes.

But add all the genes in our microbiome together and the figure comes out between two and 20 million microbial genes.

Prof Sarkis Mazmanian, a microbiologist from Caltech, argues: “We don’t have just one genome, the genes of our microbiome present essentially a second genome which augment the activity of our own.

“What makes us human is, in my opinion, the combination of our own DNA, plus the DNA of our gut microbes.”

Listen to The Second Genome on BBC Radio 4.

Airs 11:00 BST Tuesday April 10, repeated 21:00 BST Monday April 16 and on the BBC iPlayer

It would be naive to think we carry around so much microbial material without it interacting or having any effect on our bodies at all.

Science is rapidly uncovering the role the microbiome plays in digestion, regulating the immune system, protecting against disease and manufacturing vital vitamins.

Prof Knight said: “We’re finding ways that these tiny creatures totally transform our health in ways we never imagined until recently.”

It is a new way of thinking about the microbial world. To date, our relationship with microbes has largely been one of warfare.

Microbial battleground

Antibiotics and vaccines have been the weapons unleashed against the likes of smallpox, Mycobacterium tuberculosis or MRSA.

That’s been a good thing and has saved large numbers of lives.

But some researchers are concerned that our assault on the bad guys has done untold damage to our “good bacteria”.

Prof Ley told me: “We have over the past 50 years done a terrific job of eliminating infectious disease.

“But we have seen an enormous and terrifying increase in autoimmune disease and in allergy.

“Where work on the microbiome comes in is seeing how changes in the microbiome, that happened as a result of the success we’ve had fighting pathogens, have now contributed to a whole new set of diseases that we have to deal with.”

The microbiome is also being linked to diseases including inflammatory bowel disease, Parkinson’s, whether cancer drugs work and even depression and autism.

Obesity is another example. Family history and lifestyle choices clearly play a role, but what about your gut microbes?

This is where it might get confusing.

A diet of burgers and chocolate will affect both your risk of obesity and the type of microbes that grow in your digestive tract.

So how do you know if it is a bad mix of bacteria metabolising your food in such a way, that contributes to obesity?

Prof Knight has performed experiments on mice that were born in the most sanitised world imaginable.

Their entire existence is completely free of microbes.

He says: “We were able to show that if you take lean and obese humans and take their faeces and transplant the bacteria into mice you can make the mouse thinner or fatter depending on whose microbiome it got.”

Topping up obese with lean bacteria also helped the mice lose weight.

“This is pretty amazing right, but the question now is will this be translatable to humans”

This is the big hope for the field, that microbes could be a new form of medicine. It is known as using “bugs as drugs”.

Goldmine of information

I met Dr Trevor Lawley at the Wellcome Trust Sanger Institute, where he is trying to grow the whole microbiome from healthy patients and those who are ill.

“In a diseased state there could be bugs missing, for example, the concept is to reintroduce those.”

Dr Lawley says there’s growing evidence that repairing someone’s microbiome “can actually lead to remission” in diseases such as ulcerative colitis, a type of inflammatory bowel disease.

And he added: “I think for a lot of diseases we study it’s going to be defined mixtures of bugs, maybe 10 or 15 that are going into a patient.”

Microbial medicine is in its early stages, but some researchers think that monitoring our microbiome will soon become a daily event that provides a brown goldmine of information about our health.

Prof Knight said: “It’s incredible to think each teaspoon of your stool contains more data in the DNA of those microbes than it would take literally a tonne of DVDs to store.

“At the moment every time you’re taking one of those data dumps as it were, you’re just flushing that information away.

“Part of our vision is, in the not too distant future, where as soon as you flush it’ll do some kind of instant read-out and tells you are you going in a good direction or a bad direction.

“That I think is going to be really transformative.”

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Illustrations: Katie Horwich

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Exercise benefits to the brain ‘may be passed on’

Physical and mental exercise has been found to be beneficial for our brains, but scientists have now found it could also improve the learning ability of our children.

In a mouse study, researchers found the benefits gained from these activities were passed on to their offspring, despite not altering their DNA.

Further research is needed to see if this replicates in humans.

The German study is being published in the journal Cell Reports.

Exercise is recommended to keep the mind sharp in the over-50s and doing puzzles and brain training exercises has been found to delay the onset of dementia and reduce the risk of diseases such as Alzheimer’s.

Researchers from the German Centre for Neurodegenerative Diseases (DZNE) found that when they exposed mice to a stimulating environment in which they also had plenty of exercise, their offspring which they had later also benefitted.

The younger mice achieved better results in tests that evaluated their learning ability than the control group.

They also had improved synaptic plasticity – which is a measure of how well nerve cells communicate with each other and the cellular basis for learning.

They found this in the hippocampus, the area of the brain that is important for learning.

This phenomenon is known as epigenetic inheritance.

What is epigenetics?

  • Epigenetics is a growing field trying to understand how the environment interacts with genes.
  • Previously it was believed that acquired skills don’t modify the DNA sequence so therefore can’t be passed on to children.
  • But in recent years scientists have found that in some circumstances lifestyle factors such as stress and trauma in parents can affect the next generation.
  • For example, a poor diet increases the risk of disease in ourselves but also raises the risk in our children.
  • This phenomenon is known as “epigenetic” inheritance, as it is not associated with changes in DNA sequence.

    They found the benefits were conveyed through the RNA molecules that are contained in sperm, along with paternal DNA.

    “Presumably, they modify brain development in a very subtle manner improving the connection of neurons. This results in a cognitive advantage for the offspring,” said Prof AndrĂ© Fischer from DZNE.

    The researchers say that whether their findings are translatable to people needs to be determined.

    Prof Marcus Pembrey, from Great Ormond Street Institute of Child Health, said the research was an “important step” in unravelling “what, if anything, contributes to an individual’s intelligence beyond genetic inheritance and learning after birth”.

    He added: “If this system of the offspring inheriting a ‘head start’ applies to humans, it might help to explain the so-called Flynn effect, where the population IQ in industrial societies has risen every decade for the last century.”

    Prof Simon Fishel, of the private Care Fertility group, said it was a “fascinating study” providing “further increasing evidence of how we conduct our lives before we conceive our children may have consequences for our offspring”.

    He said it “opens up further the enthralling study of a ‘transgenerational inheritance’ and added: “However, there is much work to do to understand if this study can not only be replicated in mice, but other mammalian species too, and ultimately in humans.”

Why some cancers are ‘born to be bad’

A groundbreaking study has uncovered why some patients’ cancers are more deadly than others, despite appearing identical.

Francis Crick Institute scientists developed a way of analysing a cancer’s history to predict its future.

The study on kidney cancer patients showed some tumours were “born to be bad” while others never became aggressive and may not need treating.

Cancer Research UK says the study could help patients get the best care.

“We don’t really have tools to differentiate between those that need treatment and those that can be observed,” said researcher and cancer doctor Samra Turajlic.

One cancer could kill quickly while a patient with a seemingly identical cancer could live for decades after treatment.

It means uncertainty for both the patient and the doctor.

Kidney cancer

It is most common in people in their 60s and 70s. Symptoms include:

  • Blood in your pee
  • Persistent pain in the lower back or side
  • Sometimes a lump or swelling in your side

    The work, published in three papers in the journal Cell, analysed kidney cancers in 100 patients.

    The team at the Crick performed a sophisticated feat of genetics to work out the cancer’s history.

    It works like a paternity or ancestry test on steroids.

    As cancers grow and evolve, they become more mutated and, eventually, different parts of the tumour start to mutate in different ways.

    Researchers take dozens of samples from different parts of the same tumour and then work out how closely related they are.

    It allows scientists to piece together the evolutionary history of the whole tumour.

    “That also tells us where the tumour might be heading as well,” said Dr Turajlic.

    Chance to change care

    The researchers were able to classify kidney cancer into one of three broad categories:

    • Born to be bad
    • Benign
    • Intermediate

      The “born to be bad” tumours had rapid and extensive mutations and would grow so quickly they are likely to have spread round the body before they are even detected.

      Surgery to remove the original tumour may delay the use of drugs that can slow the disease.

      The benign tumours are at the complete opposite and are likely to grow so slowly they may never be a problem to patients and could just be monitored.

      The intermediate tumours were likely to initially spread to just one other location in the body and could be treated with surgery.

      Michael Malley, 72, from London, took part in the trial at the Royal Marsden Hospital after being diagnosed with kidney cancer.

      He said: “Clearly studies like these are really important for understanding how kidney cancer evolves over time, and I hope this one day leads to better treatments for patients like me.”

      There is still the challenge of figuring out how best to tailor treatments to each tumour type, and even how to perform such tests in a hospital rather than a research lab.

      The tools used in this study are being investigated in other cancers, including lung cancer.

      Dr Turajlic says: “We’ve no doubt they will be applicable to other types of cancer.”

      The studies also revealed that the earliest mutations that lead to kidney cancer were happening up to half a century before the cancer was detected.

      Sir Harpal Kumar, the chief executive of Cancer Research UK, said the study was “groundbreaking”.

      He added: “For years we’ve grappled with the fact that patients with seemingly very similar diagnoses nevertheless have very different outcomes.

      “We’re learning from the history of these tumours to better predict the future.

      “This is profoundly important because hopefully we can predict the path a cancer will take for each individual patient and that will drive us towards more personalised treatment.”

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Origin of ‘six-inch mummy’ confirmed

Tests on a six-inch-long mummified skeleton from Chile confirm that it represents the remains of a newborn with multiple mutations in key genes.

Despite being the size of a foetus, initial tests had suggested the bones were of a child aged six to eight.

These highly unusual features prompted wild speculation about its origin.

Now, DNA testing indicates that the estimated age of the bones and other anomalies may have been a result of the genetic mutations.

Details of the work have been published in the journal Genome Research.

In addition to its exceptionally small height, the skeleton had several unusual physical features, such as fewer than expected ribs and a cone-shaped head.

The remains were initially discovered in a pouch in the abandoned nitrate mining town of La Noria. From there, they found their way into a private collection in Spain.

Some wondered whether the remains, dubbed Ata after the Atacama region where they were discovered, could in fact be the remains of a non-human primate. A documentary, called Sirius, even suggested it could be evidence of alien visitations.

Genetic investigation

The new research puts those ideas to rest.

A scientific team analysed the individual’s genome – the genetic blueprint for a human, contained in the nucleus of cells.

They had already used this to confirm that the individual was human. Now, the team has presented evidence that Ata was a female newborn with multiple mutations in genes associated with dwarfism, scoliosis and abnormalities in the muscles and skeleton.

“What was striking and caused us to speculate early on that there was something strange about the bones was the apparent maturity of the bones (density and shape),” said Garry Nolan, a professor of microbiology and immunology at the Stanford University School of Medicine in California.

He told BBC News: “There was proportionate maturation of the bones, making the body look more mature despite the fact that the specimen was itself small. This discrepancy drove much of the research. So, we believe that one or more of the mutated genes was responsible for this.”

The results revealed four new single nucleotide variants (SNVs) – a type of genetic mutation – in genes that were known to cause bone diseases, like scoliosis or dislocations, as well as two more SNVs in genes involved in producing collagen.

Ata also had 10 pairs of ribs, rather than 12 – a feature that has never been seen in humans before.

“We actually believe the girl was stillborn or died immediately after birth,” said Prof Nolan.

“She was so badly malformed as to be unable to feed. In her condition, she would have ended up in the neonatal ICU.”

However, access to advanced medical care was probably unavailable in the remote Chilean region where she was found. The skeleton’s intact condition suggests it may be no more than 40 years old.

Future benefit

Prof Nolan began the scientific investigation of Ata in 2012, when a friend called saying he might have found an “alien”.

He explained: “While this started as a story about aliens, and went international – it’s really a story of a human tragedy. A woman had a malformed baby, it was preserved in a manner and then “hocked”, or sold.”

The scientists said that future studies of Ata had the potential to improve our understanding of the underlying basis of genetic skeletal disorders – with the potential to help others.

“Analysing a puzzling sample like the Ata genome can teach us how to handle current medical samples, which may be driven by multiple mutations,” said Atul Butte, director of the Institute for Computational Health Sciences at the University of California, San Francisco.

“When we study the genomes of patients with unusual syndromes, there may be more than one gene or pathway involved genetically, which is not always considered.”

Prof Nolan says further research into Ata’s precocious bone aging could one day benefit patients. “Maybe there’s a way to accelerate bone growth in people who need it, people who have bad breaks,” he said. “Nothing like this had been seen before. Certainly, nobody had looked into the genetics of it.”

He added: “I think it should be returned to the country of origin and buried according to the customs of the local people.”

Origin of ‘six-inch mummy’ confirmed

Tests on a six-inch-long mummified skeleton from Chile confirm that it represents the remains of a newborn with multiple mutations in key genes.

Despite being the size of a foetus, initial tests had suggested the bones were of a child aged six to eight.

These highly unusual features prompted wild speculation about its origin.

Now, DNA testing indicates that the estimated age of the bones and other anomalies may have been a result of the genetic mutations.

Details of the work have been published in the journal Genome Research.

In addition to its exceptionally small height, the skeleton had several unusual physical features, such as fewer than expected ribs and a cone-shaped head.

The remains were initially discovered in a pouch in the abandoned nitrate mining town of La Noria. From there, they found their way into a private collection in Spain.

Some wondered whether the remains, dubbed Ata after the Atacama region where they were discovered, could in fact be the remains of a non-human primate. A documentary, called Sirius, even suggested it could be evidence of alien visitations.

Genetic investigation

The new research puts those ideas to rest.

A scientific team analysed the individual’s genome – the genetic blueprint for a human, contained in the nucleus of cells.

They had already used this to confirm that the individual was human. Now, the team has presented evidence that Ata was a female newborn with multiple mutations in genes associated with dwarfism, scoliosis and abnormalities in the muscles and skeleton.

“What was striking and caused us to speculate early on that there was something strange about the bones was the apparent maturity of the bones (density and shape),” said Garry Nolan, a professor of microbiology and immunology at the Stanford University School of Medicine in California.

He told BBC News: “There was proportionate maturation of the bones, making the body look more mature despite the fact that the specimen was itself small. This discrepancy drove much of the research. So, we believe that one or more of the mutated genes was responsible for this.”

The results revealed four new single nucleotide variants (SNVs) – a type of genetic mutation – in genes that were known to cause bone diseases, like scoliosis or dislocations, as well as two more SNVs in genes involved in producing collagen.

Ata also had 10 pairs of ribs, rather than 12 – a feature that has never been seen in humans before.

“We actually believe the girl was stillborn or died immediately after birth,” said Prof Nolan.

“She was so badly malformed as to be unable to feed. In her condition, she would have ended up in the neonatal ICU.”

However, access to advanced medical care was probably unavailable in the remote Chilean region where she was found. The skeleton’s intact condition suggests it may be no more than 40 years old.

Future benefit

Prof Nolan began the scientific investigation of Ata in 2012, when a friend called saying he might have found an “alien”.

He explained: “While this started as a story about aliens, and went international – it’s really a story of a human tragedy. A woman had a malformed baby, it was preserved in a manner and then “hocked”, or sold.”

The scientists said that future studies of Ata had the potential to improve our understanding of the underlying basis of genetic skeletal disorders – with the potential to help others.

“Analysing a puzzling sample like the Ata genome can teach us how to handle current medical samples, which may be driven by multiple mutations,” said Atul Butte, director of the Institute for Computational Health Sciences at the University of California, San Francisco.

“When we study the genomes of patients with unusual syndromes, there may be more than one gene or pathway involved genetically, which is not always considered.”

Prof Nolan says further research into Ata’s precocious bone aging could one day benefit patients. “Maybe there’s a way to accelerate bone growth in people who need it, people who have bad breaks,” he said. “Nothing like this had been seen before. Certainly, nobody had looked into the genetics of it.”

He added: “I think it should be returned to the country of origin and buried according to the customs of the local people.”