The Economist - USA (2021-02-20)

66 Science & technology The Economist February 20th 2021

them to sex offenders.) Women are thrust

into an artificial menopause, an experi-

ence unpleasant enough that, in endome-

triosis, drugs are typically prescribed for

six months at most. Several legal cases

have been brought against drug firms by

adults who took puberty blockers for pre-

cocious puberty. They allege cognitive def-

icits, brittle bones and chronic pain in later

life, though none has made it to court.

Animal studies suggest such concerns

may be worth investigating. One 2017 study

looked at sheep, which go through a devel-

opmental spurt similar to human adoles-

cence. Sheep given puberty-blockers per-

formed worse than controls on a maze-

navigation task, suggesting their spatial

memory was inferior. A 2020 paper look-

ing at mice found, among other things,

that females given puberty blockers were

more timid in unfamiliar environments,

and gave up sooner on a “forced swim” test

that is commonly used to assess whether

anti-depressants work.

One big worry is that puberty blockers

seem to reliably lead to cross-sex hormon-

es, in what doctors call a “cascade of inter-

ventions”. The best estimate, from studies

starting in the 1970s, is that around 80% of

gender-dysphoric children who are al-

lowed to express themselves as they wish,

but who do not socially transition—change

their clothes, pronouns and the like to pre-

sent as members of the opposite sex—will,

as they grow up, become reconciled to

their biological sex. Yet puberty blockers

seem to prevent that reconciliation. In Eu-

ropean clinics that report numbers, it hap-

pens with just 2-4% of children given the

drugs. American clinics rarely publish fig-

ures, but anecdotally the picture is similar.

Such numbers led British judges to rule

that the effects of those subsequent treat-

ments should be taken into account when

assessing puberty blockers. Besides their

intended effects, such as the growth of

breasts or facial hair, cross-sex hormones

also cause side-effects. One 2018 study

concluded that females who take testoster-

one are more likely to suffer cardiovascu-

lar disease, while males who take oestro-

gen have higher risk of blood clots and

strokes. The additional risk grew the long-

er the patients remained on hormones.

Some doctors worry about osteoporo-

sis. Bone density rises sharply during pu-

berty, but blockers disrupt that process. If

they are followed by cross-sex hormones

they are very likely to impair fertility, even

if hormones are later stopped—though the

lack of studies means no one knows how

much, says Will Malone, an American en-

docrinologist and member of the Society

for Evidence-Based Gender Medicine, a

new group. If the cascade of intervention

ends with removal of the testicles or ova-

ries the result will be sterility.

Despite the uncertainties, professional

bodies have endorsed the drugs. In a 2018

position paper the American Association

of Paediatrics (aap) described “gender-af-

firmative” care as the only ethical ap-

proach. Not everyone is convinced. James

Cantor, a Canadian clinical psychologist,

published a paper accusing the aapof mis-

stating the contents of its citations, which

“repeatedly said the very opposite of what

the aap attributed to them”. (Asked for

comment, the aaprestated its position.)

Marcus Evans, a psychoanalyst, resigned

from the board that oversees gids over

worries about “experimental” treatments.

The best way to settle such disputes is

the same as in any other part of medicine: a

big, well-run clinical trial. So far, despite

soaring caseloads, and puberty blockers

having been prescribed for decades, no one

is planning to conduct one.

Palaeontology

Very, very long in

the tooth

I

n the1966 science-fiction movie “One

Million Years B.C.”, Raquel Welch and

John Richardson traverse a primitive land-

scape inhabited by dinosaurs and early hu-

mans. The film was low on science and

high on fiction: by then dinosaurs were

long dead and humans—at least, ones re-

sembling Ms Welch and Mr Richardson—

were hundreds of millennia away.

A more accurate picture of Earth’s in-

habitants at the time is now being re-

vealed. In research published in Nature, a

team of scientists led by Anders Gother-

strom, at the University of Stockholm, and

Love Dalen at the Centre for Palaeogenet-

ics, also in Sweden, describe sequencing

dnasamples from mammoths that lived

and died in north-eastern Siberia around a

million years ago.

The team’s work represents a new re-

cord, for their mammoth dnais, by some

half a million years, the oldest ever suc-

cessfully reconstituted. Extracted from

horses, bears and even Neanderthals and

Denisovans, two close cousins of modern

humans, such ancient dnahas proved an

invaluable tool for investigating the past.

Although fossils preserve the gross physi-

cal features of extinct animals, they are si-

lent about many crucial details that even

an incomplete genome can help to fill in.

The trouble with dnais that it breaks

down post mortem. The more broken-

down it is, the harder it is to sequence. Sci-

entists think that, after about 6m years, all

that would be left would be individual base

pairs, the equivalent of trying to recon-

struct a book from a heap of its constituent

letters. Under the right conditions, howev-

er, such as the extreme cold of Arctic per-

mafrost, this decay can be slowed.

Dr Dalen and his colleagues were inter-

ested in three mammoth molars extracted

in the 1970s from Siberian geological layers

that suggested great age. Samples from

each were sent to Dr Dalen’s laboratory in

2017. Having checked they had not been
      unduly contaminated by bacteria or the
      shaking hands of awe-struck palaeontolo-
      gists, strands of dnawere extracted, se-
      quenced, and dated. Whereas dnasamples
      from a living animal can run to several
      hundreds of thousands of letters, the time-
      worn mammoth samples yielded strands
      mere dozens of letters long. This is close to
      the limit of what is scientifically usable,
      says Ludovic Orlando, a biologist at the
      Centre for Anthropobiology and Genomics
      of Toulouse.
      To date a specimen, fragments of its
      dna are compared to corresponding
      chunks from known descendants. Armed
      with a few evolutionary rules-of-thumb,
      scientists can calculate how long it would
      have taken for the observed mutations to
      arise. Analysis of this sort revealed that the
      youngest molar, found near a village called
      Chukochya, was between 500,000 and
      800,000 years old. A tooth found near the
      Adycha river was from an animal that had
      died between 1m and 1.2m years ago. A
      third, found near another village called
      Krestovka, was dated at between 1.1m and
      1.2m years. The previous record had been
      held by a set of horse dnathought to be as
      much as 780,000 years old.
      The teeth held other surprises. The
      Krestovka mammoth belongs to a previ-
      ously unknown branch of the mammoth
      family tree, an ancestor of the Columbian
      mammoth which roamed North America
      1.5m years ago. The Adycha mammoth was

Million-year-old mammoth genomes

push the limits of a revolutionary

technique

Watch out, Raquel!