The Economist - UK (2019-06-29)

76 Science & technology The EconomistJune 29th 2019

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compared with 11-25% in human popula-

tions. Some participants in the whale study

were previously involved in sequencing

African and Asian elephant genomes. They

found that an important weapon in the ele-

phants’ arsenal is tp 53 , a gene that encodes

an apoptosis-inducing protein called p53.

This protein is known colloquially as “the

guardian of the genome”.

Human beings have two copies of tp 53

in their chromosomes—one from each par-

ent. Those in whom one of these does not

work manifest a condition called Li-Frau-

meni syndrome, and are almost certain to

develop cancer. Elephants’ chromosomes,

by contrast, sport 40 versions of tp 53 —part

of the explanation, surely, of why elephant

tumours are so rare.

Joshua Schiffman, a paediatric oncolo-

gist at the Huntsman Cancer Institute in

Utah who was involved in the elephant

study, is investigating how elephants’ mul-

tiple copies of tp 53 co-ordinate an attack

on mutated cells. He is also studying how

slight differences in the composition of

elephant p53 make it a more efficient mu-

tant-cell killer than its human counterpart.

The power of elephant p53 led Dr Schiffman

to co-found peel Therapeutics, based in

Utah and Israel (the firm’s name is derived

from the Hebrew word for elephant). peel’s

purpose is to translate discoveries in com-

parative oncology into human patients.

The firm’s researchers are experimenting

with minuscule lipid spheres loaded with

proteins, including synthetic elephant p53.

Their most promising experimental drug is

designed to deliver this directly to a pa-

tient’s tumour cells. Details are still under

wraps, but Dr Schiffman says that, in a lab-

oratory, introducing synthetic elephant

p53 to human cancer cells induces “incred-

ibly rapid and robust cell death”.

Compare and contrast

These studies on elephants and whales are

part of a larger effort in comparative oncol-

ogy—some of it based at Arizona State Uni-

versity’s Arizona Cancer Evolution Centre

(ace). Researchers at ace, including Dr Tol-

lis and the centre’s director, Carlo Maley,

are looking at cancer rates in 13,000 animal

species, using more than 170,000 records

of individual animals. This study is the

first of its kind, and is intended to search

for patterns that might explain resistance

and susceptibility to tumours. To this end

the researchers are casting their net wide.

They have, for example, attempted to in-

duce tumours in sponges that have no re-

ported incidence of cancer.

Dr Tollis, Dr Maley and their colleagues

will also search for tumour-suppressing

genes in previously sequenced genomes

available in public databases. These in-

clude about 65 species of mammal—some

of which, such as naked mole rats, are not-

ed for low cancer rates even though they

aresmallcomparedwithelephants and

whales,andsodonotseemtoconformto

Peto’sparadox.Thesearchwillalsolookat

non-mammalianexceptionsto thepara-

dox,suchascrocodilesandbirds.DrTollis

andDrMaleyspeculatethatbirds,atleast,

inheritedtheircancerresistancefromdi-

nosaurancestorswhichweremuchlarger.

Theyareworkingoncomputationalmod-

elstotestthishypothesis.

Onenovelaspectofallthisresearchis

itswillingnesstotaketheanimalsunder

studyontheirownterms.Medicalscience

usesanimalsa lot—butalmostalwaysthey

aretheretoactasstand-insforhumanbe-

ings,a roleencapsulatedintheword“mod-

el”thatisoftenappliedtosuchlaboratory

organisms.Comparativeoncologyexplic-

itlyrejectsthisidea.Instead,itstudiesa

phenomenon, namely cancer and the

body’sresponsetoit,withoutprejudice,

andonlythenattemptstodrawmedically

useful lessons. Whether that approach

mightbeextendedtootherfieldsofmedi-

cineissurelyworthconsideration. 7

C

ompared withmammals, living mem-

bers of the crocodile clan have excep-

tionally boring dentition. From the slen-

der-snouted gharials of India and the

nocturnal caimans of South America to the

saltwater behemoths of the South Pacific,

crocodile teeth vary little in morphology.

All are conical and pointed. Each tooth in

an animal’s mouth is almost identical to its

neighbours—as befits a group of that feed

on a mixture of fish and the occasional

careless beast that strays too close to the

shore, or even into the water itself.

This predilection for pointed fangs is

not, however, how it has always been. Dur-

ing the days of the dinosaurs, the Jurassic

and Cretaceous periods, crocodile-clan

members showed extraordinary dental

diversity. Many of their teeth have proved

so bizarre that some palaeontologists have

theorised that, far from being carnivorous,

these ancient species might have been eat-

ing plants. A study published this week in

Current Biology, by Keegan Melstrom and

Randall Irmis at the University of Utah,

confirms this. It also suggests that herbi-

vory evolved in the crocodile clan on sever-

al occasions.

When trying to work out what ancient

animals ate, palaeontologists usually look

to modern analogues. If teeth from an ex-

tinct beast match those of a modern spe-

cies, the two are quite likely to have had

similar diets. With extinct crocodilians,

however, this palaeontological tactic has

routinely been stymied because their

teeth, which are adorned with many rows

of cusps and wrinkled enamel, look noth-

ing like what is found in the mouths of ani-

mals alive today. This has left the topic of

what ancient crocodilians ate very much

up for grabs. Some palaeontologists argue

that certain species, such as Simosuchus

clarki(illustrated below in an artist’s im-

pression) were vegetarian.

To solve the puzzle Mr Melstrom and Dr

Irmis turned to Orientation Patch Count

Rotated (opcr) analysis. This technique

scans a tooth and measures the complexity

of its surfaces. Use of opcrhas demon-

strated, in a quantifiable manner, that diet

is closely related to tooth complexity. Car-

nivores tend to have simple teeth. Omni-

vores have more complex teeth. Herbivores

have the most complex teeth of all.

Until now, however, the technique has

been used mostly on the molars of living

mammals. Indeed, Mr Melstrom and Dr Ir-

mis knew of no studies that had tested it

extensively on crocodiles and their kin.

This lack of testing made sense, because

living crocodilians have no complex tooth

morphologies to analyse—so why bother?

Beware of stereotyping extinct animals

on the basis of modern examples

Palaeontology

Vegetarian

crocodiles

An old croc