The EconomistFebruary 8th 2020 Science & technology 712 cancer genome carried four or five. And
with some clever genetic archaeology they
also found that some driver mutations can
occur years before symptoms appear.
To discover this, researchers used a new
concept called “molecular time” to recon-
struct the cellular evolution of tumour
cells. By comparing the dna of cells within
tumours, the researchers could place mu-
tations in chronological order based on
how many cells they appeared in. Earlier
mutations occur more frequently. For ex-
ample, driver mutations in a gene called
tp53 were found to have originated at least
15 years before diagnosis in types of ovarian
cancer, and at least five years before in
types of colorectal and pancreatic cancer.
Driver mutations in a gene called cdkn 2 a
were found to have occurred in some lung
cancers more than five years before diag-
nosis. In theory, that provides a window in
which to find people at risk of developing
these diseases, and perhaps prevent the
cancer ever appearing.
The new study closes down talk that sig-
nificant numbers of unknown driver mu-
tations could lurk in the relatively unex-
plored regions of the human genome. One
such driver mutation in non-coding dna
was found in 2013—a mutation in the tert
gene across many different cancer types.
To check for more like this, the consortium
sequenced and analysed all the dnaletters
of these non-coding regions (which ac-
count for 98% of human dna) for the first
time. They found that non-tertdriver mu-
tations occurred at a rate of less than one
per 100 tumours in these regions.
Peter Campbell of the Wellcome Sanger
Institute in Cambridge, Britain, and a
member of the pcawgconsortium, says an
important contribution of the study is that
by sequencing so many tumours it has
raised the number of patients in whom a
genetic contribution to their cancer can be
identified from less than 70% to 95%. The
goal, he says, is for genome sequencing of
tumours to become routine. Efforts to in-
troduce this are under way in some coun-
tries, including Britain, the Netherlands
and South Korea, he adds.
Results, results, results
Insights are all very well, but what about
cold, hard clinical progress? Turning ge-
nome sequences into meaningful predic-
tors of cancer will require comparisons be-
tween samples from tens of thousands of
patients, say the researchers, along with
data on their treatments and survival rates.
Processing this would be beyond the reach
of any single organisation. Instead, a fol-
low-up project is planned that includes na-
tional funding agencies, charities and cor-
porate partners from more than a dozen
countries around the world. It aims to link
full sequences of 200,000 cancer patients
to their clinical data by 2025. 7R
ural folk can blame Aesop—of the
moralising fables—for centuries of sto-
ries that mock them as bumpkins. The an-
cient Greek storyteller’s tale of the Country
Mouse and the Town Mouse was only the
first to emphasise their supposed simpler
tastes and habits when compared with
more sophisticated urbanites. So listen for
the cheers from Somerset to Kansas as neu-
roscientists announce that, in fact, it is city
living that can dull the wits—at least when
it comes to finding one’s way in the world.
Growing up in a city, a vast global survey
has found, has a lifelong negative impact
on a person’s ability to navigate. When
looking for a half-remembered restaurant
in a poorly-lit side street, it seems Country
Mouse would be a more useful companion.
In the new study, posted to the online
repository bioRxiv, scientists led by An-
toine Coutrot at Nantes University in
France and Hugo Spiers at University Col-
lege London describe how they used a data-
set gathered from 4m players of a computer
game called “Sea Hero Quest”, which tests
way-finding skills by asking players to
memorise a map showing the location of
checkpoints and then measuring how well
players can steer a boat to find them, guid-
ed only by their mental map.
The game was released in 2016 and all
players have since been asked for basic in-
formation about themselves, including
their age, gender, home country, and
whether or not they grew up in a city.
From that database, Dr Spiers and his
colleagues examined a subset of 442,000players from 38 countries: those who had
answered all the questions and who had
played the game until they reached the lat-
er levels. He found that the strongest indi-
cator of a high score was a player’s age—
older people performed relatively poorly,
which chimes with what researchers know
about age-related cognitive decline. But
the benefit of rural living was strong
enough to offset some of that. Data from
American players showed that a 70-year-
old who grew up in the countryside had the
navigational abilities of an average 60-
year-old across the dataset.
The gap between the navigation skills of
rural and city people was largest in Ameri-
ca (about six times wider than for Roma-
nia), and the researchers think they know
why. They gave each country a complexity
score by analysing how the streets were
laid out in its largest cities. And they found
that countries dominated by simple
layouts of grid-based cities (most common
in America and Argentina) dragged down
navigation skills more than growing up in a
city based around more complicated net-
works of streets, such as Prague.
The study does not show why cities
have this impact on people growing up in
them. It cannot rule out that an external
factor, such as the effect of air pollution on
a developing brain, might play a role. But
Dr Spiers says that the brain’s navigational
abilities probably weaken in the less chal-
lenging city environment because they are
not being used as much. Although cities
may appear more elaborate, they also fea-
ture more clues to help residents find their
way, such as numbered streets. As many
city-dwellers on a visit to the countryside
can attest, one field tends to look much the
same as another, so there are fewer exter-
nal landmarks to help guide the way.Street smart
Neuroscientists already know that living
and working in more complex environ-
ments can influence the function and
structure of the brain. Brain scans of Lon-
don taxi drivers who have gained an ency-
clopaedic memory of the city’s streets by
learning “The Knowledge” show that they
tend to have an enlarged hippocampus—a
region of the brain acting as a neural gps,
sensing position and trajectory on an inter-
nal map of the environment.
The detrimental effect of city living on
navigation (taxi drivers aside) is probably
most acute in people under 16-18, Dr Spiers
says, because their still-developing brains
respond and change the most according to
external stimuli. And while people who
live in cities with young children should
not be alarmed, the study does raise some
interesting ideas for urban planners: keep
their city designs not so simple perhaps.
And for everyone else, it might be an idea to
turn off Google Maps. 7Streets with no names could weaken
the brainNeuroscienceLost in the city