Fires of life: the struggles of an ancient metabolism in a modern world

© 2001 British Nutrition Foundation Nutrition Bulletin, 26, 13–27

Correspondence: Andrew M. Prentice, MRC International Nutrition

Group, Public Health Nutrition Unit, London School of Hygiene

and Tropical Medicine, 49–51 Bedford Square, London, WC1B

3DP, UK. Tel: + 44 207 299 4682; fax: + 44 207 299 4666.

E-mail:[email protected]

BRITISH NUTRITION FOUNDATION ANNUAL LECTURE

Fires of life: the struggles of an ancient metabolism in a modern world

Andrew M. PrenticeMedical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London,UK & Medical Research Council Keneba,The Gambia

Whales, gales and the survival of the fittest

On 23rd February 1821, the captain of the whaleship

Dauphin trained his spyglass on something unusual: a

boat, impossibly small for the open sea, bobbing on the

swells.

Three months earlier, the Nantucket whaling ship

Essex was attacked in the middle of the Pacific by a

giant sperm whale: the eponymous Moby Dick. The

ship was swamped and had to be abandoned by the 22

crewmembers who boarded its three small whaling

boats. Before it sank, they were able to rescue a quan-

tity of bread and hard tack, a barrel of drinking water

and two live Galapagos giant tortoises for each boat.

They then undertook a disastrous voyage of 4 500 nau-

tical miles back to the coast of Chile. After 90 days at

sea only eight survived to tell the horrific tale of star-

vation, cannibalism and thirst.

Nathaniel Philbrick’s recent book In The Heart of theSea uses the diaries of the young cabin boy to recreate

the details of this epic tale of survival, and to argue that

those who survived relied on a combination of charac-

ter, luck and a thrifty metabolism. The evidence for the

thrifty metabolism is tenuous (the survivors were short

and stocky, and the six black crewmembers, who were

likely to have a higher muscle-to-fat ratio, all died first),

but it builds on an idea first proposed almost 40 years

ago by James Neel (1960), from the Department of

Human Genetics at the University of Ann Arbor. Neel

was struck by the relationship between diabetes and

large babies, and argued that both might result from a

‘thrifty genotype rendered detrimental by progress’. He

postulated that the periods of feast and famine that

dominated the first 99% of human life on earth would

have favoured the selection of an ability to lay down

extra adipose tissue during periods of feasting and

13

‘A grain in the balance will determine which individual

shall live and which shall die’

The Origin of SpeciesCharles Darwin

‘. . . the helmsman bought the ship as close as possible to

the derelict craft. Even though their momentum quickly

swept them past it, the brief seconds during which the ship

loomed over the open boat presented a sight that would

stay with the crew the rest of their lives.

First they saw bones – human bones – littering the

thwarts and floorboards, as if the whaleboat were the

seagoing lair of a ferocious, man-eating beast. Then they

saw two men. They were curled up in opposite ends of the

boat, their skin covered with sores, their eyes bulging from

the hollows of their skulls, their beards caked with salt and

blood. They were sucking the marrow from the bones of

their dead shipmates.’

Excerpt from the preface of In the Heart of the SeaNathaniel Philbrick

gorging, and that this survival trait from ancient times

had become worse than redundant in the face of abun-

dant food.

The ‘thrifty gene’ concept was later extended by

Neel’s disciples to account for the extraordinarily high

levels of diabetes in many Polynesians. The Naruan

islanders, displaced from their traditional lifestyle by

phosphate-mining companies that stripped their island

of its thick layers of guano, have world record levels

of obesity and diabetes. In this, they compete with

other Polynesians and with the Pima Indians from

Arizona who have also been displaced from their

traditional lifestyle. It is argued that the founding

members of Narua and other far-flung atolls would

have had to survive perilous sea voyages in which pro-

visions may have run out well before landfall. For the

few that made it, many would have perished on the high

seas. The survivors of those journeys would be those

whose metabolism was best suited to starvation. They

could have started the journey as the fattest members

of the crew, or their metabolism might have been

exceptionally frugal in times of shortage, or both. In

short, they possessed a thrifty gene and passed this

down through a genetic bottleneck of a few founding

members.

The thesis of this lecture is that the ‘thrifty gene’

hypothesis can be extended far beyond the unusual cir-

cumstances of Polynesia, and that the current epidemic

of obesity is partly caused by the fact that we all possess

an ancient metabolism selected to protect us from

starvation, and hence, quite unsuited to our modern

lifestyle. My realisation that the metabolisms of most of

humankind have been honed by famine and starvation

was prompted by two recent experiences.

DNA: a recipe for life the length of 800 bibles

The first of these revelations occurred in our Gambian

laboratory, when I was using some of my own blood to

practise a method for extracting DNA. As the silken

DNA appeared, I marvelled at the fact that these tiny

threads contained a record of the history of my fore-

bears, an indelible record of their struggle for survival.

The DNA that each of us possess is a recipe for our con-

struction; a recipe that has been moulded and altered

through the ages, tested by the harshest of critics and

rejected more often than not, tweaked here and there by

the processes of evolution, adding some ingredients and

removing others before being passed from generation to

generation.

As I wondered at the significance of those minute

14 Andrew M. Prentice


In our modern society, this may not seem so remark-

able. After all, spontaneous abortions are infrequent,

neonatal deaths are relatively rare, and infant deaths are

rarer still. Most of us survive to adulthood and are

fertile, and most could find a mate if we seriously put

our mind to it, but it was not always so. Malnutrition

and disease exerted a stringent test against which only

the fittest survived.

In The Gambia, among the cluster of villages where

we work, the elders have kept records of births and

deaths since 1950. These reveal that, before we intro-

duced comprehensive health and nutrition programmes

in the mid-1970s, fewer than half the children lived

to see their fifth birthday. (The figure, incidentally, is

now well over 90%). This appalling statistic of child

mortality recorded just a few decades ago only gives a

measure of post-natal deaths. Add to it the estimated

50–80% embryo loss soon after conception, the spon-

taneous abortions and stillbirths, and we see that every

adult who ever lived to reproduce in this inhospitable

setting was a success story. They possessed elements of

a formula that set them apart from all their brothers and

‘It may be said that natural selection is daily and hourly

scrutinising, throughout the world, every variation, even

the slightest; rejecting that which is bad, preserving, and

adding up all that is good; silently and insensibly working,

whenever and wherever opportunity offers, at the improve-

ment of each organic being’.

The Origin of Species(Charles Darwin)

threads, I was struck by the realisation that every single

one of our forebears has survived to the age of repro-

duction. By definition, this must be the case, or they

would not be our forebears. Is this a banal statement of

the obvious? Or is it a rather profound thought? Take

a moment to reflect on its implications.

If we only look back as far as the point at which our

evolutionary tree split from our nearest relative, we will

have travelled back over a quarter of a million genera-

tions. In each and every one of these, our forebears sur-

vived from the moment of their conception until they

themselves provided the sperm or egg to start the cycle

again. Sometimes they only survived by the skin of their

teeth, but survive they did. Each of us is the product of

hundreds of thousands of generations of winners; mil-

lions if we extrapolate back through our non-human

ancestors to Darwin’s ‘primordal form into which life

was first breathed’.

Fires of life: an ancient metabolism in a modern world 15


sisters who died from hunger and disease, and were able

to pass on a survival kit of robust genetic traits by means

of their DNA.

Crossing vast oceans by canoe

The second revelation occurred in Dunedin at an exhi-

bition of the work of one of New Zealand’s most

famous artists, Charles Goldie. One of Goldie’s best-

known pictures is a large, harrowing canvas entitled

The Arrival of the Maoris in New Zealand. It depicts

the starving voyagers from far Hawaiki at the moment

when, hopeless and desperate, they catch a glimpse of

land through a break in the storm. My first thought was

that this was a perfect pictorial representation of Neel’s

thrifty gene hypothesis, but I was to be disappointed.

The Maoris themselves consider the painting to be

simply a creation of the artist’s mind (and indeed it was

painted by Goldie when at the Académie in Paris, as an

exercise based on Géricault’s Raft of the Medusa in The

Louvre). They argue that there is no record in their oral

history that their forefathers arrived in Aotearoa in such

severe straits. The historian Tahana Pango Wahanui

described it as ‘insulting to the Maori people and their

ancestors’ mastery of the sea’.

Polynesians, we must face up to the fact that there is

little historical support.

My first reaction was to find this thoroughly disap-

pointing; it seemed yet another case of facts spoiling a

nice theory. However, further reflection shows that the

Polynesian story is probably an irrelevant distraction in

what is a much more far-reaching, and hence more im-

portant story, namely, that we all possess metabolisms

that have been moulded by famine. We possess an ancient

metabolism selected to function in quite a different

setting, one that has been fashioned to maximise survival

when the forces of nature or warfare empty the granaries.

Famine: the most pervasive selectivepressure?

In order to persuade you that hunger and famine have

been an ever-present influence on genetic selection, a

most horrible and savage tale must be told; one of

unimaginable miseries regularly punctuating the more

prosperous passages of man’s history. As you sit com-

fortably and replete reading this article, it is worth

taking a moment to reflect fully on the true horror of

the words famine and starvation. Even to most of us

who have never experienced true hunger in our whole

lives, they evoke a shudder of subconscious memory.

‘The lowering sky and dark weary waste of the waters over

which the weather-battered canoe is making its way

conveys the idea of utter loneliness, and brings into sharp

relief the glint of sunshine which shows to the exhausted

watchers in the canoe the first, faint indication of land. But

it is on the barque itself and those in it that the attention

dwells first and last. There is a terrible attraction in these

naked emaciated figures huddled in all different postures

of agony in the canoe. Famine and despair are writ large

over all those scarecrows of human beings. Their ribs may

be counted, showing through the thin covering of flesh,

their limbs are those of skeletons, and there is a world of

terrible meaning in the contortions of their bodies. The

picture is certainly most gruesome.’

Art critic of The New Zealand Graphic describing

Charles F. Goldie’s epic painting The Arrival of theMaoris in New Zealand

So far as we can tell, the Maoris are probably correct

to assert that the ancient Polynesians were masters of

the seas, who could navigate with precision and were

quite capable of sustaining extremely long voyages

without running short of food. However tempting

it is to apply Neel’s thrifty gene concept to today’s

‘I am mourning on my high throne for the vast misfortune,

because the Nile flood in my time has not come for seven

years! Light is the grain; there is a lack of crops and of all

kinds of food. Each man has become a thief to his neigh-

bour. They desire to hasten and cannot walk. The child

cries, the youth creeps along, and the old man; their souls

are bowed down, their legs are bent together and drag

along the ground, and their hands rest in their bosoms. The

counsel of the great ones in the court is but emptiness. Torn

open are the chests of provisions, but instead of contents

there is air. Everything is exhausted.’

The Stella of FamineChiselled into Egyptian rock in the time of

Tcheser about 2000 bc

In an appendix to their two-volume book on TheBiology of Human Starvation, published in 1950, Ancel

Keys and colleagues list the dates of over 400 histori-

cally documented famines. It is difficult to contemplate

the horror of 400 major famines, and yet, they claim

only to have scratched the surface. They assert that their

list must be considered far from complete, particularly

for all parts of the world except the British Isles, North-

western Europe, and the Mediterranean basin. In Asia,

the traditional home of the famines, only India has been

covered by any more than a casual examination of

the historical records. Purely local famines have been

omitted, except in a few cases, when they have involved

notable conditions and have been unusually well docu-

mented. Nor have they included those periods of food

scarcity, which, although attended by great suffering

and elevated mortality, did not produce real famine con-

ditions. Most of the famines caused directly by military

action have also been omitted.



infectious diseases. These dense populations are initially

sustainable, but in time suffer Malthusian collapses,

brought on by a variety of possible factors. The first

is that they simply outgrow the productive capacity

of the land (a threat which still hangs over the world

today), and that this triggers a breakdown of traditional

farming practices which, in turn, leads to land ruin

and disaster. The second is that climatic change sud-

denly alters the balance of energy supply and demand

with similarly catastrophic effects. Joseph’s interpreta-

tion of the Pharoah’s dream as indicating 7 years of

plenty followed by 7 years of scarcity reflects just such

a scenario: ‘And, behold, there came up out of the river

seven kine, fatfleshed and well favoured; and they fed

in a meadow: and, behold, seven other kine came up

after them, poor and very ill favoured and lean fleshed,

such as I never saw in the land of Egypt for badness:

and the lean and the ill favoured kine did eat up the first

seven fat kine: and when they had eaten them up, it

could not be known that they had eaten them; but

they were still ill favoured as at the beginning.’ And the

seven ears of corn ‘full and good’ were devoured by the

seven bad ears ‘withered, thin, and blasted with the east

wind’.

‘All of Upper Egypt was dying of hunger, to such a degree

that everyone had come to eating his children . . . the entire

country had become like a starved grasshopper . . .’.

Description of famine in Egypt 2180–60 bc in

The Sepulchers of Ankhtifi

Such historical records reveal that famine has been

with mankind throughout the world and from time

immemorial. Famine comes in many forms and for

many reasons. Our hunter–gatherer ancestors were used

to feasts and famines, depending on the seasons, the

movements of animals, and the skill and fortune of the

hunt. They lived in small groups and were prepared

to move long distances when conditions deteriorated.

As such, they were probably relatively immune to the

sort of catastrophic famines that periodically devastate

agrarian populations, but nonetheless, an ability to

rapidly lay down a store of fat when food was plentiful

would have been a beneficial survival trait.

‘If there be a cutting down of the food offerings of the gods,

then a million men perish among mortals, covetousness is

practiced, the entire land is in a fury, and great and small

are on the execution block.’

Middle Kingdom Hymn to the Nile

The catastrophic famines that have wiped out large

proportions of many populations have their origins in

agriculture and in the vagaries of the weather. It was

the agrarian revolution that formed the basis of the

great civilisations of the world, but it was also the agrar-

ian revolution that led to the greatest human catastro-

phes. Farming allowed population density to escalate

rapidly in spite of the retarding effect of mortality from

‘And there was famine in the land:

And Abram went down into Egypt to sojourn there:

For the famine was grievous in all the land’

Abram’s journey into Egypt Genesis 12

In Floods, Famines and Emperors, Professor Brian

Fagan chronicles the effects of climate on the fate of

civilisations. Fagan argues that the downfall of many

great civilisations was caused by climatic changes driven

by the phenomenon of ‘El Niño’; from the Pharoahs of

Egypt to the Moche of Peru, and from the Mayans of

Tikal to the Anasazi of North America. These civilisa-

tions arose in times of plenty when the climate favoured

population growth to beyond the true carrying capacity

of the land. It only took a few years of drought, or a

single storm, to sweep away the topsoil, and starvation

led to an irreparable collapse in population numbers

and the end of the civilisation. Archaeological evidence

indicates that this is a pattern that has occurred again

and again, and historical evidence backs it up. Even the

great Roman Empire was affected at times with reports

of thousands of starving Romans throwing themselves

into the Tiber in 436 bc.



Countries such as India and China have suffered

endemic famine. Researchers in the 1930s discovered

documentary evidence that between 108 bc and 1911

ad there were no fewer than 1828 major famines

in China. Hungry Ghosts by Jesper Becker describes

how a famine culture has been passed down through

Chinese history with advice as to which wild vegetation

can be eaten, what should be sold first to raise money,

and which members of the family should be sacrificed

before others. Cannibalism has been so rife that entire

books have been written about it. When the Han

dynasty was established over 2000 years ago amidst

enormous upheaval, it was recorded that nearly half the

people in the empire died of starvation. This prompted

the founding emperor Gao Zu to issue a proclamation

in 205 bc authorising people to sell or eat their children

if necessary. These gruesome stories are quoted here to

underscore the severity of famine. Reports of cannibal-

ism, especially of children, occur in almost all major

famines.

mother’s empty breast. Today’s junk mail contains an

appeal from Concern labelled ‘8 million still face star-

vation in Ethiopia – Urgent action needed to save lives’.

CNN carries pictures of monsoon flooding in Northeast

India and Bangladesh that has wiped out the rice crops

and made millions homeless. Even in today’s world of

United Nations emergency organisations and relief non-

governmental organisations, the spectre of famine still

haunts the world’s poor.

The examples used above were from ancient writings,

deliberately selected to emphasise that famine has a long

history, but the 20th century has seen some of the most

fearful famines. Many were caused by droughts, floods

or unseasonal frosts. Many more had their origins in

human conflict, political folly, administrative incompe-

tence, greed and corruption.

‘One could scarcely see the water in the Vistasa, entirely

covered as the river was with corpses soaked and swollen

by the water in which they had long been lying. The land

became densely covered with bones in all directions until

it was like one great burial ground, causing terror to all

beings.’

Kashmir in the years 917–18 AD, as related in

Kalhana’s Rajatarangini

China 594 bc:

‘. . . in the city we are exchanging our children and

eating them . . .’

The Siege of the Chong Capital by the Cho Army

Famine in the 20th century

No doubt, some readers will be thinking that this dev-

astation occurs elsewhere both in time and place; that

it has no relevance to today’s wealthy commuter return-

ing home from the metropolis to a good dinner. The

issue of time can be dealt with swiftly. As you read this

sentence, millions of people worldwide are short of food

and hundreds of thousands, perhaps millions depending

on nature’s throw of the dice this week, are starving.

Today’s paper carries a front-page advertisement from

Oxfam with a sorrowfully thin infant clinging to its

‘The causation of famine by unkind nature was by far

the most common until fairly modern times, when man’s

dominance of nature allowed him to assume the role of

creator of his own misery.’

The Biology of Human StarvationAncel Keys

In World War II, starvation conditions appeared in

many parts of the world. Greece suffered between May

1941 and April 1943 when increased mortality and

decreased births depleted the population of Athens and

Piraeus by over 60 000. The total loss for the country

was estimated at 450 000, and many countries fared

much worse. For instance, India rapidly felt the effects

of the Japanese occupation of Burma, Indo-China and

the East Indies, which prevented the export of rice from

these highly productive regions.

Stalin’s Terror Famine 1932–33Intentional genocide of 7 million Ukrainians

‘. . . 20 souls for every letter of this book . . .’

The Harvest of Sorrow Robert Conquest

Russia has suffered appallingly from famines in the

twentieth century. In 1906, 22% of the population was

affected. Five years later, famine affected 25 million, and

1919 marked the start of 5 years of food shortages for

which the US provided $60 000 000 for relief. In World

War II Russia suffered, and again at the break-up of the

Soviet Union, but the worst by far was Stalin’s Terror

Famine of 1932–3. As part of the soviet collectivisation

campaign, the regime unleashed a man-made famine in

Ukraine and the neighbouring Cossack lands. All food

stocks were forcibly requisitioned, a military cordon

prevented food supplies from entering, and the popula-

tion was left to die in a famine organised as a genoci-

dal act of state terrorism.



the silent emergency of North Korea kept hidden from

western eyes for many years.

The case being made is that famine has been, and

remains, a pervading threat to humanity, and so far I

have not even started to mention Africa, the cradle of

humankind, and the original source of all of our genes.

Africa, a continent that ranges from lush abundance to

the barely habitable regions of the Sahel and the Horn

of Africa. Historical sources from Africa go back less

far but even so, are sufficient to record 14 great famines

in Sudan spanning from 1543 to 1795. Many African

languages contain a broad lexicon of phrases describing

the different levels of hardship. No doubt, it is from

Africa that your most vivid images of famine will be

drawn; from TV news footage of the Biafran War in

Nigeria, of feeding camps in Ethiopia, and of long trails

of gaunt refugees in Sudan.

The Siege of Leningrad

The 900 days

Sept 1941 – Jan 1944

3 million trapped in Leningrad

>>630 000 starved to death.

‘Here lies half the city . . .’

Poet Sergei Davydov’s description of the

Piskarevsky Cemetry

China suffered major famines in 1916 and in 1929,

when 2 million people died in Hunan Province alone.

The Japanese invasion and the subsequent Kuomintang

rule heralded further starvation, with grain prices

increasing 70-fold overnight and inflation rising to

2 870 000% by the end of 1948. Yet, none of these com-

pared with the catastrophic mortality caused by Mao’s

‘Great Leap Forward’ when peasants were forced to

melt their agricultural implements and cooking pots

to make steel. The leadership blamed the cause on

‘unprecedented natural calamities’ and on Russian insis-

tence on the repayment of a large loan, neither of which

was true. Readers of Wild Swans (Chang 1993) may

recall the chapter ‘Capable Women Can Make a Meal

Without Food’. This Maoist slogan was a grotesque

reversal of the ancient Chinese saying ‘No matter how

capable – a woman cannot make a meal without food’.

Jung Chang’s accounts of her parents eating chlorella

grown in their own urine as a cure for famine oedema,

and of executions of traders caught selling the meat of

babies and children as wind-dried rabbit, remind us of

the terrible exigencies necessary to survive under condi-

tions of severe famine.

The Spanish Civil War, the Korean War, the Ameri-

can bombing in Southeast Asia, the war in Kampuchea,

the Khmer Rouge regime of Pol Pot, and many more

examples of our human folly, all created mass hunger

and starvation affecting tens of millions. Even without

the help of warfare, famine has eroded the strength and

numbers of many populations in Asia, from India to

Ci Kworiya – eat calabash

Kumumuwa – the great suffering

El Commando – the commander

Memories of past famines in African oral history

A brief history of famine in Britain . . .

The majority of English family trees, except the most

aristocratic, will soon trace their roots back to simple

peasants vulnerable to food shortages, for that is what

most people were in the Middle Ages. Using Ancel Keys’

(1950) table of famines we can pick at random a gen-

eration of our ancestors and examine the historical

record to see whether they were hungry. Ten generations

back takes us to 1740 when Keys lists ‘England,

2 years’. The next entry for England is 1748. Another

10 generations earlier takes us to 1540, the reign of

Henry VIII. In 1540 there was famine in Sardinia, not

England, but we need only trace our finger down the list

to 1545 to find the first entry for England, then 1549,

1556 (3 years), 1563 (London), 1563 (Britain) and so

on. If we go further back to 1321, sometimes called

the last great famine in England, we will have skated

over a further 15 entries, or roughly one per generation

(Fig. 1).

If 1321 is described as the last great famine, this

implies that there were other great famines previously,

and so there were. The 1321 famine followed worse

famines in 1315–16 and another crop failure in 1319.

The famine was caused by an ecological disaster trig-

gered, as so often, by the fact that the population had

outgrown the carrying capacity of the land. Contempo-



rary records tell us that, amongst other factors, firewood

became so scarce that cow dung, instead of being spread

on the land as manure, was dried on the walls of Peter-

borough as fuel; a practice that can still be seen in

villages from Pakistan to Tibet.

The year 1286 heralded the start of 23 years of

scarcity with true famine in 1289 and 1294. In both

1235 and 1257, it is recorded that over 20 000 people

died of starvation and its attendant disease in London

alone. This was a substantial proportion of the popula-

tion at the time. By 1270, King Henry III wrote an order

to the city coroner demanding that the streets be cleared

more quickly of the corpses of those who had died

from starvation. Travelling further back, the desolation

caused by the Norman Conquest of 1066 started 9 years

of famine in which cannibalism was widely reported.

In 1042, there was a 7-year famine and in 976, the

micla hungor of John of Brompton. As history recedes

towards the Roman invasion we pass over another 22

documented famines in England, many with records of

cannibalism to authenticate the severity. This is about

as far as our historical record goes, but we can only

assume that conditions were at least as bad in the pre-

history of England.

Each of these occurrences was a widespread famine

of sufficient note to enter the historical record. Imagine

how many other crises hit the various counties and

villages, and how many poor families suffered terrible

hardship when conditions were marginal; a hardship of

enduring anguish as their women failed to conceive and

their infants starved to death. A hardship leaving no

mark in history; except perhaps on our genes. A mark

that has suddenly revealed itself as obesity now that

natural famines have been banished from England and

replaced by plenty.

a

Fig. 1(a,b) A small selection of recorded famines in Britain. (Source: AncelKeys et al. The Biology of Human Starvation)

b

‘People ground and chopped many unsuitable things into

bread; such as mash, chaff, bark, buds, nettles, leaves,

hay, straw, peatmoss, nutshells, peastalks, etc. This made

people so weak and their bodies so swollen that innumer-

able people died. Many widows, too, were found dead on

the ground with red hummock grass, seeds which grew in

the fields, and other kinds of grass in their mouth. People

were found dead in the houses, under barns, in the ovens

of bath houses and wherever they had been able to squeeze

in, so that, God knows, there was enough to do getting

them to the graveyard, though the dogs ate many of the

corpses.’

Contemporary report of Swedish famine in 1597

. . . and elsewhere in Europe

This was the history of famine in England alone. A

similar story could be told for any European country.

Indeed, many of the English famines were themselves

part of a wider picture.

Ice cores from Greenland, and glaciation records from

as far afield as Chamonix or the Frans Josef Glacier

on South Island New Zealand tell the story of the

Little Ice Age; 500 years of abnormally cold weather

which ended in the late 19th century. Prior to this, the

Medieval Warm Period had allowed Norwegian farmers

to grow wheat north of Trondheim, Scottish farmers to

grow crops up to 425 metres above sea level, and vines

to flourish at 200 m in Herefordshire. Then, for reasons

that still remain unexplained, the Little Ice Age wrought

havoc around the world. At the climax of the Little

Even the warmer countries of middle and southern

Europe have seen their share of famine. The famine

of 1319 lay right across Europe, being harshest in

Germany, Flanders and France, where cannibalism was

once again rife. Whether from ‘all windes and ill

weather’ or from the ravages of war, many a European

had reason to complain that ‘the hand of God is heavy

upon us’, and on more than one occasion, it changed

the course of history.



North America: the home of obesity but a stranger

to famine?

North America is one of the only regions to have been

spared mass famine in recent centuries, not withstand-

ing the profound hardship engendered by the Great

Depression. So, how do we reconcile this with the fact

that the United States today leads the world in obesity

statistics? The question needs to be looked at separately

for the indigenous population (the Indians, now few in

number), and for the colonisers and immigrants.

The extraordinary high levels of obesity among the

Pima Indians have already been mentioned. The Pimas

are the descendants of the Hohokam whose culture

centred in the desert lands of southern Arizona and

northern Sonora in 700 AD. They farmed maize, beans,

squash and cotton, and possibly tobacco and amaranth.

By the sedentary period (900–1200 AD), they had devel-

oped canals up to 16 km long to channel the winter run-

off from the Gila River, creating irrigation schemes that

allowed two crops a year. This canal system was modi-

fied and improved over a thousand years, and evidence

of a highly advanced Hohokam culture can be seen at

the excavations in Snaketown. However, by 1400 AD,

many of the Hohokam sites had been abandoned and

the population collapsed, leaving a small number of

founders for today’s Pima tribe. The cause of the col-

lapse is uncertain. Were they wiped out by the fierce

nomadic Apaches, or did a sudden climatic change dry

out the canals and bring famine to the land? Floods,Famines and Emperors argues that it was famine caused

by El Niño that brought these great cultures to their

knees, or at the very least, caused the dispersion that

Ice Age in the mid-1600s, the glacier above Les Bois

advanced by ‘over a musket shot every day, even in

August’. In Europe it was Scotland, Finland, Norway,

Sweden and the Baltic States, countries where the

northern latitude puts them at extra risk of fearsome

winters and failed summers, that suffered most. As

London partied on the frozen Thames, the Scots suf-

fered grievously, with one-third of the upland popula-

tion dying in the years leading up to the union with

England in 1707.

‘Parents killed their children and children killed parents,

and the bodies of executed criminals were eagerly snatched

from the gallows’

Contemporary report from Flanders at the beginning of

The Great Famine in 1319

‘Qu’ils mangent de la brioche’

Marie-Antoinette’s (almost certainly apocryphal)

response to the bread shortages that sparked the French

Revolution

In Citizens – A Chronicle of the French Revolution,

Simon Schama describes how, on 13th July 1788, a hail-

storm burst over much of central France from Rouen as

far south as Toulouse with ‘stones so monstrous they

killed hares and partridge and ripped branches off elm

trees’. In the Île-de-France, where fruit and vegetable

crops were wiped out, farmers wrote, ‘A countryside,

erstwhile ravishing, has been reduced to an arid desert’.

In much of France a drought followed, and that, in turn,

was followed by a winter of a severity the like of which

had not been seen since 1709, when the red Bordeaux

was said to have frozen in Louis XIV’s goblet. Frozen

rivers prevented mills from turning what grain there was

into flour and people were reduced to boiling tree bark

‘The region has been visited by the exterminating angel.

Every scourge has been unloosed. Everywhere I have found

men dead of cold and hunger.’

Mirabeau’s report from a visit to Provence immediately

prior to the French Revolution

to make gruel. The thaw brought further misery by

flooding the fields and pastures of the Loire valley. These

events contributed to the unrest leading up to the storm-

ing of the Bastille by the enraged peasantry, but even the

dearth of 1789, ‘la disette’ as it was known, was only

the little sister of the famine 80 years earlier, in which

roads were littered with starved corpses.



then made them vulnerable to attack. A similar story

could be told about today’s Pecos and Hopi Pueblo

Indians, descended from the great Anasazi culture, the

Papagos from the Hohokam, and the Zuni Pueblo who

retain elements of the Mogollon culture.

As for the Pilgrim Fathers and the many other earlier

settlers from Britain, they would have brought with

them sets of genes that had survived the 151 famines

recorded in Britain between the birth of Christ and the

time that the first of them set sail in the 1600s. The same

argument could be made for immigrants from else-

where; they would bring with them their history faith-

fully chronicled in their DNA. If the inscription on the

Statue of Liberty is anything to go by – ‘Give me your

tired, your poor, Your huddled masses yearning to

breathe free, The wretched refuse of your teeming shore

. . .’ – then it is especially likely that those who had

endured poverty and hunger, and survived it, would

have been concentrated by the attractions of the vast

new land.

Many of America’s early immigrants may have

brought thrifty genes with them. The appalling con-

ditions of the slave caravans from the interior of West

Africa, the misery of the holding centres at Ile de Goré,

and the horrific slave ships of the Middle Passage

with their massive mortality are likely to have selected

out the strongest and fittest; those able to keep walking,

to endure hunger and thirst, to survive disease, and

to avoid being murdered. This transportation would

be just an intermediate step in Darwin’s ‘struggle for

existence’. It followed thousands of years of survival

on the fringes of the Sahara in the African interior,

and was immediately followed by man-made selection,

as the fittest and plumpest slaves fetched the highest

prices and were bought up by the owners of the best

estates, where they might have a better opportunity to

flourish.

And then, we have the Irish. The Irish Potato famine

was one of the most terrible for which detailed docu-

mentation exists. Readers who are interested in the

administrative and political background to a famine

that need not have happened should read Cecil

Woodham-Smith’s excellent account The Great Hunger– Ireland 1845–1849, from which I have drawn much

that follows. For the purposes of our current investiga-

tion, however, the political details are of little relevance.

What matters is whether it is likely that the Great

Hunger created the natural selection of thrifty genes that

may now be penalising the descendants of the mass emi-

gration, and those with whom they mixed their Gaelic

genes in subsequent generations.

The Irish famine was certainly grievous. Famine

oedema was widespread throughout the country.

Commander Caffyn, in his report on Skull wrote that

although three-quarters of the population were skele-

tons, nevertheless, swelling of the limbs was universal.

In Killala, it was reported that people ‘swell up and are

carried off at once’. In Skibbereen, Elihu Burritt saw

men whose bodies were swollen to twice their natural

size still labouring on the public works.

As in all famines, children especially suffered and

faded silently away in vast numbers. Sidney Godolphin

Osborne, later one of Florence Nightingale’s helpers in

the Crimea, visited workhouses and infirmaries and

described the state of the children in details too pitiful

to be repeated here at any length – ‘in the very act of

death still not a tear nor a cry. I have scarcely ever seen

one try to change his or her position . . . two, three or

four in a bed, there they lie and die . . .’.

To any American Irish of today interested in their

genetic makeup, it is who survived that matters, not

who died. It is whether the Irish émigrés who flocked

across the Atlantic carried with them a high concentra-

tion of thrifty genes skimmed from the surface of the

mass of humanity who left their Irish fields. In the spring

of 1846, the first failure of the potato crop produced

a superior sort of emigrant, consisting of well-to-do

persons. Unhappily, the situation was soon to change.

Ships started to bring tenants forced to emigrate by their

landlords, and arriving penniless. It was a trickle that

soon turned into a flood. Unscrupulous ticket brokers

sold passages on unseaworthy vessels that were to

become known as ‘coffin ships’. The Passenger Acts in

force at the time were drafted under the instructions that

‘I ventured through the parish this day to ascertain the

condition of the inhabitants, and, altho’ a man not easily

moved, I confess myself unmanned by the intensity and

extent of the suffering I witnessed especially among the

women and little children, crowds of whom were to be seen

scattered over the turnip fields like a flock of famishing

crows, devouring the raw turnips, mothers half naked,

shivering in the snow and sleet, uttering exclamations of

despair while their children were screaming with hunger.

I am a match for anything else I may meet here, but this

I cannot stand.’

From a letter written on Christmas Eve 1846 by a

Captain Wynne to his superior officer in County Mayo

quoted in Cecil Woodham-Smith’s The Great Hunger –

Ireland 1845–1849

they should not increase the cost of the passage, and

they set lax criteria for space, ventilation, and provi-

sioning. Each passenger was supposed to be supplied

with 7 pounds of provisions per week and 3 quarts of

water per day, but these were rarely met.

After the United States effectively closed its borders,

most ships set sail instead for British North America,

the St Lawrence and Quebec. Here occurred one of the

most terrible disasters in North American history. As the

winter of 1846–47 turned to spring, ‘famine fever’ was

added to starvation among the arriving cargo of human

misery; the famine fever that had caused infinite misery

in Ireland itself had now become ‘ships’ fever’. Famine

fever included two separate diseases, typhus and relaps-

ing fever, both of which were transmitted by lice and

found ideal conditions among the filthy crowded

conditions of the ships’ holds and in human hosts

whose immune systems were suppressed by starvation.

The authorities in Quebec had a quarantine station

on Grosse Isle in the St Lawrence with beds for 150

patients, but soon after the winter ice had receded to let

in the first ships of 1847, Grosse Isle had 695 persons

in hospital and 164 on board ship waiting to be taken

off.

By the end of May, there were thirty-six moored

vessels, all with cases of fever and dysentery, containing

13 000 emigrants. A few days later, the line of ships was

2 miles long and a further 45 000 emigrants at least were

expected. Despite being at sea for weeks without food

or sufficient water, the authorities refused to allow

the ships to unload and sent them no assistance. The

screams for food and water to quench the unbearable

thirst caused by the fever, and the conditions leading to

‘a stream of foul air issuing from the hatches as dense

and as palpable as seen on a foggy day from a dung

heap’, were ignored.

Eventually, the attempt at quarantine was abandoned

and there started a continuous procession of ships to

Grosse Isle where ‘Hundreds were literally flung on the

beach, left amid mud and stones to crawl on the dry

land as they could’. Boat-loads of dead were taken four

times in a day from single vessels.

These deaths are only part of the story. Even before

their arrival, the mortality at sea had been great. The

Larch sailed from Sligo with 440 passengers, of whom

108 died at sea; the Virginius with 476 passengers, of

whom 158 died on the voyage and 106 were landed

sick. The delay of several days before the starving,

thirsty and sick were permitted to disembark from the

marooned ships was fatal for many. The Agnes, for

instance, which had arrived with 427 passengers, had

only 150 alive after the quarantine of 15 days.



And to any who survived these horrors, equal misery

was to follow. The new immigrants became fugitives as

Quebec, Montreal and Toronto were overrun with the

destitute and starving Irish. Many travelled south ille-

gally. An estimated 37 000 arrived in Boston in 1847

alone to swell the existing population of 114 000. In

New York, 52 946 Irish landed legally to say nothing

of the others who flooded in by land. New York and

Boston largely managed to control the epidemics of

cholera and ship fever that threatened to break out, but

in Canada, the situation was another disaster. After a

summer of epidemics on land, the enfeebled, emaciated

and almost naked Irish – ‘like ghosts not men’ – had to

endure a Canadian winter. These were the unpromising

beginnings that still stain the memory today.

The bare statistics for North America, as best as they

can be estimated, suggest that over a hundred thousand

left Ireland in 1847. By the end of that year, 20 000 had

died in Canada alone and at least 17 000 on the voyage

over. In the ensuing years, most of the Irish had been

reduced to beggars and vagrants and suffered mortality

rates far higher than any other groups.

Boston Census 1841–45: 61.55% of Irish Catholic chil-

dren died under 5 years. The average age of death recorded

in St Augustine’s cemetery was 13.43 years.

‘Children seem literally born to die . . .’

Lemuel Shattuck

Returning to the problem of modern-day obesity, we

must ask what the effects of this terrible tragedy might

have been on the genetic constitution of anyone today

who claims to have Irish blood in them. It is important

to make the point that famine cannot create thrifty

genes in a Lamarkian manner, it would merely select any

that happen to have arisen by chance. Any trait whose

origins were locked into the genetic make-up of an Irish

peasant and which favoured their survival under the ter-

rible conditions of the Great Hunger would tend to be

preserved, and any wasteful traits would be erased from

the genetic blueprint. The filtration effect of the famine

would have been considerable. Final estimates of mor-

tality suggest that a loss of at least two and a half million

people had taken place, amounting to about 25% of

the pre-famine population. To this should be added the

further selection that would have resulted from sup-

pressed fertility and from the appalling child mortality

in the Irish ghettos for many generations after.



This distressing tale of the Great Hunger is just one

small example of the many genetic bottlenecks that may

have been imposed on American ancestors before they

first set eyes on their new found land. It would be foolish

to suggest that the Irish famine alone is the root cause

of American obesity, but the argument can be made

that the affluent Manhattan banker of today, whatever

his antecedents, carries in every nucleus a metabolic

memory of famine and how best to survive it. The

Pilgrim Fathers who set sail in the Mayflower on 16 Sept

1620 create a fitting allegory. They suffered terrible

mortality during the first two winters when their inex-

perience of the new conditions led to almost total crop

failure and the loss of all their seed corn. The feast of

Thanksgiving commemorates the deliverance of the

survivors, but in modern America, a perpetual state

of feasting is bringing new perils to an unaccustomed

metabolism.

In past decades, this rainy season crisis caused a

huge increase in the number of infants with severe

protein–energy malnutrition. Malnutrition and disease

increased the mortality in young children by 6-fold com-

pared to the dry season, and over 50% of them died

before their fifth birthday.

How many of these deaths were caused by hunger?

About half were caused by malaria, which seems to be

no more common in underweight children, but malnu-

trition was almost certainly a contributory factor in the

remainder. Thus, year on year, nature preserved the

favoured individuals; those carrying genetic variations

giving them resistance to malaria or other infections,

and those best able to grow on the frugal rations avail-

able to them. If we assume that in the past one-half of

the children died, and in one-half of these, their death

was related to malnutrition, then this amounts to an

exceptionally powerful selective drive in favour of a

thrifty genotype.

In the middle ages England suffered an annual

‘hungry gap’ whose end was celebrated on the 1st

August with Lammas Day (hlaf-maesse = loaf mass),

and countries at higher latitudes suffered even greater

contrasts between feasts and famine. Similar scenarios

have been occurring year in and year out around the

world.

The Voyage of the Mayflower 1620

From 104 passengers, only 23 left any descendants

‘. . . the fales of their grounds which came first over in the

Mayflower according to their loses were cast . . .’

‘. . . the greatest halfe dyed in the general mortality . . .’

Governor Bradford’s Journal

Seasonal food shortages

The argument made above is that catastrophic famines

have winnowed out unthrifty genes, but there may have

been another selection effect with an even more perva-

sive influence, namely, the seasonal food shortages asso-

ciated with winters (in high latitudes) and dry seasons

(in temperate and tropical zones). Again, the effects of

these can be gleaned from both the historical record and

contemporary observations.

‘In the preservation of favoured individuals and races,

during the constantly-recurrent struggle for existence,

we see the most powerful and ever-acting means of

selection’.

The Origin of SpeciesCharles Darwin

‘Nin I kono faata, I si kumbo, kaatu fo i si naa konko’

(When your stomach is full you should mourn – as it

will soon be empty)

Mandinka proverb from rural Gambia

Seasonality dominates the lives of subsistence farming

communities such as those in The Gambia. With a single

well-defined rainy season, it is only possible to gather

one crop per year. Prior to the gathering of this crop at

the end of the rains, the villagers suffer a ‘hungry season’

as they start to run short of last year’s staples. Both men

and women lose weight in the hungry season; the extent

of which depends on the state of the previous year’s

harvest. In a bad year, the weight loss will be 5 or 6 kg.

This represents about 50% of the body fat of an average

woman. If the new crops were to fail at this stage, the

people would already be half-way to famine. This is

why food emergencies in Africa hit with such savage

rapidity.



However, there may be other reasons to continue the

search for thrifty genes, as they may provide valuable

insight into other physiological processes, particularly

those related to reproduction and fetal growth.

The human genome contains over 30 000 regions that

are either known genes, or have sequences suggesting

that they are likely to be genes. Simple experiments with

differential display chips indicate that over 6000 of

these are significantly induced by the consumption of a

meal, of which only a small proportion have been

described and from which an even smaller proportion

were previously thought to be involved in energy me-

tabolism. Where do we start searching for the elusive

‘thrifty genes’ in such a haystack? In planning the strat-

egy, it may be helpful to ask which genes are likely to

exert the greatest selective advantage in times of famine.

The answer is almost certainly those that aid concep-

tion and the survival of the fetus.

It is now well known that hunger and thinness in the

mother inhibits conception. Several decades ago Rose

Frisch developed the idea that a decline in conceptions

is a natural response to the energy deficit caused by

hunger, and to the body’s loss of fat. Fat loss drives

down the hormone leptin which, in turn, regulates the

reproductive hormones. Leptin acts as a woman’s

fuel gauge. Low levels send a subconscious message

to the brain that her body is in no fit state to risk

the additional energy drain that would result from

conception.

Frisch’s hypothesis seems to hold up well when tested

against famine. In The Gambia, a graph of the seasonal

frequency of births in the villages we study describes

an elegant wave pattern, with a peak of 305 births per

month in November to January and a trough of 210

births in May and June, a drop of 31%. The low point

comes exactly 9 months after the worst months of the

hungry season.

The Gambian example of hunger-suppressed fertility

has frequently been replicated in the more severe

conditions of true famine. In 1944, the Nazi blockade

of Western Holland caused the Dutch Winter Famine

when energy intake was estimated to be less than

700 kcal/day. In Rotterdam, midwives saw their clien-

tele dwindle from the usual 250 per week to just 85 per

week 9 months after the lowest food rations. The same

was seen in the Siege of Leningrad, where the birthrate

at the State Pediatric Institute dropped steadily from

447 per month in early 1940 to just 13 per month in

late 1942. During the severe famine of 1877 in Madras,

there were only 39 births in the relief camps even though

100 000 people were cared for over many months. In

Hunger is a recurrent theme in 14th century England

according to Piers Ploughman . . .

‘Then hunger leapt at Waster and seized him by the belly,

wringing his guts until the water ran from his eyes. And

he gave the Frenchman such a drubbing that he looked as

lean as a rake for the rest of his life. He pasted them so

soundly that he almost broke their ribs; and if Piers hadn’t

offered hunger a pease-loaf and besought him to leave off,

by now they’d both be pushing up the daisies!’

. . . and there are clear descriptions of the struggle to

survive each hungry season . . .

‘And with these few things we must live till Lammas time,

when I hope to reap a harvest in my fields . . . Then can I

spread you a feast as I’d really like to.’

Piers PloughmanWilliam Langland

On the possible nature of thrifty genes

For almost 2 decades, scientists have been searching for

evidence that obesity may be caused by a thrifty metabo-

lism that allows certain individuals to get by on a lower

energy supply, and hence, to deposit unwanted energy

as fat even though they may be consuming a similar

amount to their neighbour. The search has been largely

fruitless, and in spite of the discovery of new families of

uncoupling proteins that could form the basis of energy-

sparing or energy-profligate mechanisms in muscle and

other tissues, there is little evidence that obese people

have an inherently more efficient way of utilising energy.

Most attention is now focused on genes that may alter

the regulation of appetite and the subsequent metabolic

disposal of the excess energy that is now a daily feature

of modern life. Neel’s hypothesis originally visualised

that it was in this domain that the thrifty gene or genes

were likely to operate, by releasing a greater amount of

insulin that favoured the storage of energy as fat, and

possibly stimulated appetite. In the modern world, the

search for such ‘susceptibility’ genes for obesity has

become almost a contradiction in terms because many

populations display rates of overweight well in excess

of 50% in spite of most people’s best attempts to avoid

weight gain. This is perhaps further evidence in support

of the concept that humans have evolved general mech-

anisms favouring fat storage and that most people carry

such traits. Under these circumstances, the search for

‘unthrifty’ genes might become more profitable as a

means to understanding how our metabolism attempts

to regulate energy balance.



the surrounding regions, the birth rate fell from a usual

value of 29 per 1000 to just 4 per 1000.

A fascinating historical analysis of burials, births and

christenings in Cumberland and Westmorland during

the famines of 1597 and 1623 shows a similar picture

(Figs 2,3). In his book Famine in Tudor and StuartEngland, Andrew Appleby (1978) uses church records

from the parish of Crosthwaite around Keswick to

describe the impact on life and death. Burials increased

5-fold to over 250 per year in each of these famines. In

the first famine, births dropped from 105 to 55, and in

the second from 105 to 35; marriages declined some-

what later. He then analysed what happened in 1646; a

year of bubonic plague. The increase in burials was

similar but there was no decline in births; in fact, there

was a slight rise. The decrease in fertility, he concludes,

was a direct result of the hunger rather than of the stress

associated with a local catastrophe (Figs 2,3).

Thus, any factor that helps a mother conceive during

periods of hunger would put her genes at an advantage

over those of a less fertile woman, and the most obvious

way for this to operate is simply for her to be consid-

erably fatter at the onset of famine; a manifestation of

thrifty genes.

Conception is only the first step to the successful

propagation of genes. A second type of advantage

would accrue if there were genes that assisted the

embryo and fetus to survive even when the mother was

in dire nutritional straits. Figure 4 illustrates the little-

appreciated fact that it is in this pre-natal period that

there is a much greater selective pressure on our genes

than after birth. It shows the average attrition rate for

ova progressing from their unfertilised state to the pro-

duction of another healthy and fecund man or woman.

It shows that the odds of any one ovum successfully pro-

Fig 2 The effects of famine on population dynamics. Extracted from churchrecords in Crosthwaite Parish near Keswick. (Source:Andrew Appleby Faminein Tudor and Stuart England)

Fig 3 The effects of plague on population dynamics. Extracted from churchrecords in Crosthwaite Parish near Keswick. (Source: Andrew Appleby Faminein Tudor and Stuart England)

Fig 4 Natural selection of thrifty reproductive genes. (Data from varioussources)

ducing a grandchild (considered a reasonable proxy of

having achieved reproductive success) is approximately

0.0007–1. Perhaps pregnancy is where we should con-

centrate the search for thrifty genes?

Any mother who has inherited a metabolic trick to

spare energy for her growing fetuses, allowing them to

be bigger at birth, will enhance the prospects for all her

offspring. Any individual fetus that has inherited the

trick of persuading its mother to part with more nutri-

ents even when she is malnourished will enhance its own

survival chances so long as it does not compromise the

mother so much that she cannot breastfeed it after birth.

There is evidence that both of these factors may be at

play.

In comparisons of the metabolic adaptations that

occur in pregnancy in women in England and The

Gambia, we have demonstrated that the Gambian

mothers show a remarkable ability to turn down their

metabolic rate following conception and hence, to

sustain a pregnancy with a minimal increment in energy

needs.

With respect to fetal growth, the originator of the

thrifty gene hypothesis, James Neel, was put on to his

idea by the well-known link between diabetes and birth-

weight; diabetic mothers tend to have overgrown

babies. This was customarily viewed as being a resultof the mother’s diabetes. Instead, Neel reasoned that

both the diabetes and high birthweight might each be a

manifestation of a thrifty gene.

The growth of a fetus is controlled by a host of dif-

ferent genes, each influencing metabolism in different

ways. At the time of writing, four of these have been

shown to have variant forms in humans (polymor-

phisms), which alter birthweight. Interestingly, each is

linked to energy metabolism. The glucokinase gene

affects fetal growth in an intriguing and powerful way,

but the variants are very rare. There is also a mito-

chondrial gene (MT16189) that influences birthweight.

This is interesting because mitochondria (the cell’s

power station) are passed down only from the mother,

but its effects appear not to be very strong. The gene

for a signalling protein (the G-protein b3 subunit) also

influences birthweight and metabolic efficiency, but the

jury is still out regarding its potency.

The most common gene variant so far known to affect

birthweight is the INS VNTR (insulin variable-number-

of-tandem-repeats). David Dunger, John Todd and

colleagues in Cambridge have shown that a common

mutation of INS VNTR increases a baby’s weight,

length and head circumference. It also affects postnatal

growth. They speculate that it represents a thrifty gene

and are studying populations around the world to see



Postscript

As a postscript, I should point out that until research-

ing the material for this lecture I had never considered

myself an advocate of the thrifty gene. I viewed it as a

nebulous and ill-defined concept entirely lacking in any

proof. Having now seen the profound impact that

famine has exerted on the survival of our forebears, and

hence on their metabolism, I am forced to modify this

view, slightly. The thrifty gene remains a nebulous and

ill-defined concept entirely lacking in any proof, but it

has now become a very intriguing one.

Acknowledgements

I am indebted to numerous people for their contribu-

tions to stimulating discussions on the likely role of

famine in human evolution especially Ann Prentice

(MRC Human Nutrition Research), our daughters

Claire and Sarah, Joann McDermid, Liz Poskitt and

Tony McMichael (London School of Hygiene and

Tropical Medicine), David Dunger and Virpi Lummaa

(University of Cambridge), Susan Jebb (MRC Human

Nutrition Research), and Bakary Dibba and Landing

Jarjou (MRC Keneba). Claire Prentice (University of

Oxford) conducted much of the medieval literature

research.

Further reading

Aberth J (2000) From the Brink of the Apocalypse: ConfrontingFamine. War, Plague and Death in the Later Middle Ages Routledge, London.

Appleby A (1978) Famine in Tudor and Stuart England. Liverpool

University Press, Liverpool.

Becker J (1997) Hungry Ghosts. Mao’s Secret Famine Free Press,

New York.

Braun JV, Teklu T & Webb P (1999) Famine in Africa. Causes,Responses and Prevention Johns Hopkins University Press,

Baltimore.

whether it is more heavily represented where hunger has

been a recent phenomenon.

The story is a complex one and far from solved, but

it may provide the first glimpse of a candidate gene to

fulfil Neel’s prediction made almost 40 years ago.

‘The evolution of higher animals directly follows . . . from

the war of nature, from famine and death . . .’

Concluding remarks in Charles Darwin’s

The Origin of Species



Chang J (1993) Wild Swans Flamingo, London.

Conquest R (1987) The Harvest of Sorrow. Soviet Collectivisationand the Terror-Famine Oxford University Press, Oxford.

Darwin C (1989) (originally 1859) The Origin of SpeciesWordsworth Editions Ltd, London.

Diamond J (1997) Guns, Germs, and Steel: The Fates of HumanSocieties WW Norton, New York.

Drumm M (1998) Famine Trocaire, Dublin.

Fagan B (2000) Floods, Famines and Emperors Pimlico, London.

Frisch RE (1982) Malnutrition and fertility. Science 215: 1272–3.

Harrison ES (2000) The 900 days: The Siege of Leningrad Pan,

London.

Jordan WC (1996) The Great Famine. Northern Europe in theEarly Fourteenth Century. Princeton University Press, Princeton.

Keys AJ, Brozek J, Henschel O, Michelson O & Taylor HL (1950)

The Biology of Human Starvation. University of Minnesota Press,

Minnesota.

King J (1987) The Mayflower Miracle – The Pilgrims’ Own Story ofthe Founding of America David & Charles, Hong Kong. (see also

www.mayflower.org and www.mayflowerfamilies.com).

Lacey R & Danziger D (2000) The Year 1000: What Life Was Likeat the Turn of the First Millenium Abacus, London.

Langland W (1970) (originally 14th century). Piers PloughmanPenguin Books, London.

Neel JV (1960) Diabetes mellitus: a ‘thrifty’ genotype rendered

detrimental by ‘progress’. American Journal of Human Genetics14: 353–62.

O’Connor TH (1997) The Boston Irish Black Bay Books, Boston.

Philbrick N (2000) In the Heart of the Sea HarperCollins, London.

Sen A (1983) Poverty and Famines. An Essay on Entitlement andDeprivation Oxford University Press, Oxford.

Schama S (1989) Citizens: a Chronicle of the French RevolutionPenguin Books, London.

Various (1999) The Great Famine and the Irish Diaspora inAmerica University of Massachusetts, Minnesota.

Various (2000) Obesity (Nature Insight Series). Nature 404: 631–

77.

Woodham-Smith C (1962) The Great Hunger. Ireland 1845–1849Penguin Books, London.

The above are just a fraction of the relevant material. Readers with a

deeper interest can insert the key-word ‘Famine’ in any good univer-

sity library (e.g. www.lib.cam.ac.uk/ Catalogues/OPAC/) or the British

Library (www.bl.uk which requires registration).

Documents

Fires of life: the struggles of an ancient metabolism in a modern world