After
a remarkable analysis of bacterial DNA from 1,000-year-old mummies,
scientists have proposed a new hypothesis for how tuberculosis arose and
spread around the world.
The
disease originated less than 6,000 years ago in Africa, they say, and
took a surprising route to reach the New World: It was carried across the Atlantic by seals.
The new study, published Wednesday in the journal Nature, has already provoked strong reactions from other scientists.
“This
is a landmark paper that challenges our previous ideas about the
origins of tuberculosis,” said Terry Brown, a professor of biomolecular
archaeology at the University of Manchester. “At the moment, I’m still
in the astonished stage over this.”
But
Helen Donoghue, an expert on ancient DNA at the University College
London, rejected the idea that tuberculosis could have emerged so
recently. “It just cannot be right,” she said, citing earlier fossil
evidence of the disease.
Tuberculosis
has long been one of the deadliest diseases. In 2012, 8.6 million
people became ill with this infection, and it caused 1.3 million deaths,
according to the World Health Organization. The invading bacterium,
Mycobacterium tuberculosis, attacks the lungs, where it causes
widespread scarring.
To better understand the disease, a number of scientists have worked for decades to reconstruct its history.
In
some people who get tuberculosis, the bacteria attack the skeleton, and
archaeologists have found signs of tuberculosis damage in bones dating
back centuries. Other scientists have examined DNA from different
strains of the bacteria, using the mutations in different lineages to
draw its family tree.
But archaeological studies and genetic research have often reached different conclusions about the disease’s origins.
Some
scientists have argued that tuberculosis spread from cows to humans
when the animals were first domesticated 10,000 years ago. Others have
argued that the disease is far older, having evolved about 70,000 years
ago, and spread from humans to cows and other animals.
The
geographical distribution of the disease has also puzzled scientists.
Tuberculosis strains found today in the New World are closely related to
strains from Europe. That genetic link suggests that colonists brought
the bacteria with them.
But
archaeologists have found human bones with telltale signs of
tuberculosis that date back centuries before Columbus’s arrival.
In
2012, a group of archaeologists and geneticists joined forces,
searching for tuberculosis DNA in samples of bones from 68 sets of New
World remains.
The
scientists failed to find tuberculosis DNA in most of the specimens,
but they succeeded in finding genetic material in three 1,000-year-old
mummies from the Chiribaya culture of southern Peru.
The
scientists retrieved many fragments of DNA from each mummy — so many,
in fact, that they could recreate the entire genome of the bacteria in
each victim. Before this new study, the oldest tuberculosis genome was
reconstructed from a woman who died in Hungary in 1797.
The Peruvian genomes held two surprises.
The
scientists expected that the tuberculosis DNA would be most closely
related to some particular human strain of the disease. Instead, they
found that it was most closely related to animal strains.
When
they expanded their search, they found that the most closely related
DNA belonged to tuberculosis strains found only in seals.
“We
had not thought about seals at all,” said Kirsten I. Bos, a
postdoctoral researcher at the University of Tubingen and lead author of
the new paper.
The second surprise came when Dr. Bos and her colleagues used the genomes to estimate when tuberculosis first evolved.
Over
many generations, bacteria accumulate mutations at a clocklike rate.
Understanding that the Chiribaya bacteria were 1,000 years old, the
scientists were able to estimate how many mutations the bacteria
accumulate in a year, establishing its “molecular clock.”
They used this clock to determine the age of the common ancestor of all the tuberculosis strains in their study.
Dr.
Bos and her colleagues ultimately estimated that tuberculosis was less
than 6,000 years old — much younger than most scientists had thought.
In
the new paper, the team proposes that humans acquired tuberculosis in
Africa around 5,000 years ago. The disease spread to people across the
Old World along trade routes. Meanwhile, Africans also spread the
disease to animals such as cows and goats.
Seals
that hauled out onto African beaches to raise their pups became
infected. The bacteria then spread through seal populations until
reaching South America. Ancient hunters there became infected when they
handled contaminated meat.
There
is some circumstantial evidence in support of the idea. Seals have
given tuberculosis to cows grazing on beaches, and even to zookeepers.
And archaeological remains from South America show that pre-Columbian
hunters got tapeworms and other pathogens from seals.
Dr.
Bos and her colleagues can’t say whether the tuberculosis in the
Chiribaya mummies came directly from seals, or even if the bacteria
spread from person to person. Nor can the scientists yet say whether the
strain spread into North America through human contact.
Dr.
Donoghue found the idea of hunters picking up tuberculosis from seals
“quite feasible,” but she pointed to fossil evidence suggesting that
tuberculosis is far older than 6,000 years.
In Israel, for example, archaeologists have found 9,000-year-old human remains that contain molecules produced by the bacteria. In a Wyoming cave, they have found 17,000-year-old bison bones with similar markers.
“I
think they should be rapped over the knuckles for ignoring work that
contradicts their conclusions a bit,” Dr. Donoghue said of the new
study.
Result Filters
Neurology. 2014 Jan 7;82(1):41-8. doi: 10.1212/01.wnl.0000438216.93319.ab. Epub 2013 Dec 4.
Effects of Bacille Calmette-Guerin after the first demyelinating event in the CNS.
Ristori G1, Romano S, Cannoni S, Visconti A, Tinelli E, Mendozzi L, Cecconi P, Lanzillo R, Quarantelli M, Buttinelli C, Gasperini C, Frontoni M, Coarelli G, Caputo D, Bresciamorra V, Vanacore N, Pozzilli C, Salvetti M.
Abstract
OBJECTIVE:
To evaluate Bacille Calmette-Guérin (BCG) effects after clinically isolated syndromes (CIS).METHODS:
In a double-blind, placebo-controlled trial, participants were randomly assigned to receive BCG or placebo and monitored monthly with brain MRI (6 scans). Both groups then entered a preplanned phase with IM interferon-β-1a for 12 months. From month 18 onward, the patients took the disease-modifying therapies (DMTs) that their neurologist considered indicated in an open-label extension phase lasting up to 60 months.RESULTS:
Of 82 randomized subjects, 73 completed the study (33 vaccinated and 40 placebo). During the initial 6 months, the number of cumulative lesions was significantly lower in vaccinated people. The relative risks were 0.541 (95% confidence interval [CI] 0.308-0.956; p = 0.03) for gadolinium-enhancing lesions (the primary endpoint), 0.364 (95% CI 0.207-0.639; p = 0.001) for new and enlarging T2-hyperintense lesions, and 0.149 (95% CI 0.046-0.416; p = 0.001) for new T1-hypointense lesions. The number of total T1-hypointense lesions was lower in the BCG group at months 6, 12, and 18: mean changes from baseline were -0.09 ± 0.72 vs 0.75 ± 1.81 (p = 0.01), 0.0 ± 0.83 vs 0.88 ± 2.21 (p = 0.08), and -0.21 ± 1.03 vs 1.00 ± 2.49 (p = 0.02). After 60 months, the cumulative probability of clinically definite multiple sclerosis was lower in the BCG + DMT arm (hazard ratio = 0.52, 95% CI 0.27-0.99; p < 0.05), and more vaccinated people remained DMT-free (odds ratio = 0.20, 95% CI 0.04-0.93; p = 0.04).CONCLUSIONS:
Early BCG may benefit CIS and affect its long-term course.CLASSIFICATION OF EVIDENCE:
BCG, as compared to placebo, was associated with significantly reduced development of gadolinium-enhancing lesions in people with CIS for a 6-month period before starting immunomodulating therapy (Class I evidence).Comment in
- BCG vaccine for clinically isolated syndrome and MS: infections and protective immunity. [Neurology. 2014]
- Multiple sclerosis: disease activity is reduced in CIS after BCG vaccination. [Nat Rev Neurol. 2014]
- PMID:
- 24306002
- [PubMed - indexed for MEDLINE]
- PMCID:
- PMC3873620
- [Available on 2015/1/7]
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