LIFE & EVOLUTION
Fossil shakes up
Primates reached Madagascar
in two waves, study suggests
BY BRUCE BOWER
In one published swoop, an ancient fossilized fruit bat has turned into a lemur.
If the finding holds, it suggests that
lemur ancestors made two tricky sea
crossings from Africa to Madagascar, not
one as scientists have assumed.
A new fossil analysis finds that the
species Propotto leakeyi, which lived
in East Africa between 23 million and
16 million years ago, was not a bat, as
scientists thought, but a primate closely
related to modern aye-ayes. These
strange-looking lemurs are found only
on Madagascar along with another
closely related lemur lineage.
What’s more, Propotto teeth and jaws
display key similarities with fossils of a
roughly 34-million-year-old primate,
Plesiopithecus teras, previously found
in Egypt, researchers say. Plesiopithecus
was an ancestor of Propotto and aye-ayes, the researchers conclude. Together,
the findings, published August 21
in Nature Communications, may help
rewrite lemurs’ evolutionary history.
The work challenges a long-standing
view that all modern lemurs, including
aye-ayes, evolved from a single population of African ancestors that somehow
These digital reconstructions show tooth
similarities between modern aye-ayes, which
are found only in Madagascar, and two proposed aye-aye ancestors from mainland Africa
(Propotto and Plesiopithecus).
BODY & BRAIN
New treatment is the first
based on RNA interference
BY LAUREL HAMERS
A Nobel Prize–winning discovery — that
small double-stranded RNA molecules
can silence genes by interrupting the
translation of DNA’s instructions into
proteins — is finally delivering on its
On August 10, the U.S. Food and Drug
Administration approved the first drug
that takes advantage of this natural biological process, called RNA interference.
The drug, called patisiran, targets a rare
hereditary disease that causes misshapen
proteins to build up in patients’ nerves,
tissues and organs, causing loss of sensation, organ failure and even death.
Hereditary transthyretin amyloidosis,
also known as hATTR, affects about
50,000 people worldwide. Patisiran will
help the subset of patients who have
The drug uses specially designed
pieces of RNA to silence a mutated
gene that, when active in the liver, is
responsible for patients’ symptoms.
In an 18-month clinical trial, patients
who received patisiran injections every
three weeks showed a slight decrease in
neurological symptoms; patients on the
placebo worsened overall. It’s not a cure,
but the treatment prevents peripheral
nerve disease from progressing.
This approval is “just the beginning,”
says Craig Mello of the University
of Massachusetts Medical School in
Worcester, who codiscovered the process of RNA interference, or RNAi
(SN: 10/7/06, p. 229). Other drugs using
the same approach, for diseases ranging
from hemophilia to HIV, are winding
through clinical trials.
As a medical treatment, “what makes
RNA interference so special is that it’s
biology, tested by 3 billion years of evolution,” says Phillip Zamore, a biologist
at UMass Medical School. He is also a
cofounder of Alnylam Pharmaceuticals,
the Cambridge, Mass.–based company
that makes patisiran.
RNA interference helps control when
and where genes are active. When a gene
is turned on, the information that it contains is transcribed into single-stranded
messenger RNA, or mRNA, which
translates DNA’s instructions into proteins. Small pieces of double-stranded
RNA that don’t carry protein-making
instructions can target and bind to specific mRNA molecules and flag them for
destruction, heading them off before
they make proteins.
Patisiran and other RNAi-based thera-pies in development use specially crafted
snippets of synthetic RNA to artificially
manipulate genes’ activity.
But translating the RNAi discovery into clinical applications has been
challenging. “The thing about RNA
interference that made it really attractive is the theoretical simplicity of it,”
says biologist John Burnett of City
of Hope National Medical Center in
Duarte, Calif., who has been working on
using RNA interference to target HIV.
“Of course, nothing is as simple as we
anticipate.” It took years to figure out
how to deliver such drugs to the right
place in the body to reduce harmful
off-target side effects and how to design
synthetic RNA molecules that don’t
degrade before they do their job.
Once there’s a way to safely and effectively deliver a small piece of RNA to a
specific organ, it’s easy to switch up the
RNA molecule to target a different gene
in the same organ, Mello says. He predicts
that a wave of similar RNAi-based drugs,
especially ones like patisiran that target
genes in the liver, will soon be available.
“What an amazing process it’s been to
uncover the mysteries of these mechanisms that are shared by plants and
yeasts and worms,” Mello says. “To
go from the basic biology to a drug in
20 years is kind of amazing.” s 2 mm