How to Feed the World

"How to Feed the World

By Vaclav Smil

Viking, 272 pages, $30

With Robert F. Kennedy Jr. installed as the Health and Human Services secretary, the U.S. food system is set to face intense scrutiny from policymakers in both parties.

Americans today are saddled with high rates of obesity and the chronic diseases it triggers.

At the same time, new wonder drugs have become available that have helped millions of Americans shed weight.

Entering the discussion is Vaclav Smil, the author of "How to Feed the World," which provides big-picture perspective on the global food system -- covering history, nutrition, economics, agronomy and much else. The book's title might suggest that Mr. Smil is the latest in a long line of thinkers -- dating back to Thomas Malthus in 1798 -- to predict that the world is on the precipice of food shortages. Instead, he cites reams of evidence to show that famine is not imminent. He also points out that Malthus became less pessimistic after a few years and cheekily observes that "Malthus was not a 'Malthusian' after all."

Mr. Smil, a professor emeritus at the University of Manitoba, has been writing about food for five decades. He has also produced more than 40 books about topics encompassing energy, the environment and demographics. He describes "How to Feed the World" as "a focused, strongly quantitative evaluation of the basics" of the global food system and starts out by imagining how humans would function in a world without farming.

One scenario would have humans follow the daily routine of chimpanzees, who spend valuable time and energy searching for different foods, with an emphasis on fruits. If humans had to do this, says Mr. Smil, the consequences would be dire: "It is hard to imagine how an existence centered on fig-picking would eventually lead to writing, the Parthenon, and antibiotics."

The onset of farming about 12,000 years ago, Mr. Smil writes, created a more stable food supply, which in turn curtailed the need for daily foraging and enabled people to converge in areas that eventually became cities. "Today's global civilization," he says, "rests, undoubtedly, on edible grains. Their cultivation was -- and remains -- our only option."

Moving to the present day, Mr. Smil brings sober analysis to the global food system and suggests "incremental changes" that he thinks can help to meet future challenges. He argues that in much of the world the problem is not too little food but too much, which leads to high rates of food waste.

Mr. Smil proposes that restaurants reduce portion sizes, which in the U.S. have grown sharply over the decades, in part because there's little marginal cost increase associated with larger servings. He also recommends reducing the volume of food produced, which in many countries greatly exceeds what is needed to feed their populations, as well as limiting consumer choice: "There is surely no need for American supermarkets to carry 40,000-50,000 different items of food," he writes.

As these ideas suggest, Mr. Smil doesn't seem to care about the popularity or feasibility of his proposed solutions. And he is skeptical that humans will modify their eating habits -- particularly when it comes to vegan or paleo diets. The author claims he is not focused on the kind of innovations we're often told will revolutionize the food system, but he nonetheless spells out why some of them are flawed or destined to fail.

He eviscerates organic farming as "the most radical of all unlikely solutions aimed at securing enough food by the mid-century." Synthetic fertilizers are not permitted under organic-farming standards. But banning them, Mr. Smil notes, would mean being unable to feed 40% of humanity. And yields on organic crops tend to be 25% lower than conventional ones, which translates into needing to farm much more land.

Another much-cited accusation against the present food system is that it contributes to climate change. Mr. Smil mostly steers clear of the connection. But he expresses a contrarian view about the rising concentrations of carbon dioxide in the atmosphere. More carbon dioxide, he says, has benefited plants and "resulted in indisputable biospheric greening."

Portions of "How to Feed the World," written in spare and data-heavy prose, are likely to lose the casual reader -- there's a dense chapter, for instance, devoted to the complexities of photosynthesis.

There are also major omissions, such as any discussion of weight-loss drugs like Ozempic or Wegovy, which are now being taken by up to 12% of American adults.

Users of those drugs are eating less and eating healthier, which has the potential to upend the global food system.

It would have been enlightening to hear Mr. Smil's thoughts on the topic.

The author also glosses over what is the most pressing issue with the world's food supply and a big, fat target for Mr. Kennedy: the way in which it has contributed to high rates of disease, disability and death.

One comprehensive study has found that diet is responsible for nearly 20% of the world's premature mortality. Surely that merits some discussion in a book about the global food system.

Mr. Smil declares: "I am not a pessimist or an optimist, I am a scientist." But he tends toward optimism and believes there's going to be enough food for the global population beyond 2050. And after that? He predicts that a combination of declining population and scientific progress will enable the world's food needs to be met. Malthus would likely agree.

---

Mr. Rees is the founder of Geonomica, a senior fellow at Dartmouth's Tuck School of Business and the editor of Food and Health Facts." [1]

 Each of us now builds the Parthenon every day and invents antibiotics, with a 1 in 5 chance of dying from the food we eat. Chimpanzees eat natural food and don't have this problem. What a sacrifice we have made for the sake of civilization. And cockroaches, who will be the only ones to survive the end of our civilization, will have a very green Earth because of the global heat and the abundance of carbon dioxide in the air that we have caused. Beautiful.

1.  Feast Or Famine. Rees, Matthew.  Wall Street Journal, Eastern edition; New York, N.Y.. 10 Mar 2025: A15.

 

CRIPR panaudojimas moksle

 „2010-ųjų pabaigoje Šanchajaus laboratorijoje gimė aštuonios makakos beždžionės. Iš pradžių jos atrodė panašios į kitus kolonijos kūdikius, tačiau netrukus išryškėjo skirtumai. Naktimis jos buvo daug aktyvesnės nei jų bendraamžiai. Jų hormonai taip pat neįprasti. Melatoninas, kuris paprastai svyruoja kartu su dienos ir nakties hormonu, buvo stresas ir padeda miegui. amžinai aukštas. Tada jų elgesys pasikeitė: jie ilgą laiką sėdėjo sustingę kampuose, išsigandę bėgo nuo savo prižiūrėtojų ir pradėjo palaidoti savo mažas galvas – tai psichikos ligos požymiai.

 

 Jų negalavimo priežastis buvo genetinis eksperimentas. Kai beždžionės buvo vienaląsčiai embrionai, mokslininkai naudojo CRISPR redagavimo įrankius, kad nutildytų arba „išmuštų“ geną, padedantį reguliuoti vidinį kūno laikrodį. Jo sutrikimas yra susijęs su psichikos ligomis, tokiomis kaip bipolinis sutrikimas, kurį, žinoma, sunku ištirti genetiniu ir molekuliniu lygmenimis. Labai nemalonus Šanchajaus makakų gyvenimas yra dalis pastangos suprasti, kaip genai formuoja smegenų sutrikimus, ir sukurti jiems vaistus.

 

 Tai buvo galima padaryti naudojant senas technologijas, tačiau tai būtų buvę daug pastangų reikalaujanti. Mokslininkai gali išvesti išmušimus naudodami „genų taikymą“ – tai labai neefektyvus procesas, kurio metu DNR pirmiausia įterpiama į kamienines ląsteles, o paskui į embrionus. Pelėms tai užtrunka metus. CRISPR gali atlikti darbą per mėnesį. Tas pats pasakytina ir apie genetinių mutacijų pridėjimą arba „įsilietimą“. Manipuliacijos tiek gyvūnais, tiek ląstelėmis tapo tokios greitos ir lengvos, kad mokslininkai gali modeliuoti daugybę ligų laboratorijoje, atskirti sudėtingus genetinius mechanizmus ir sukurti didžiulius tyrimus, siejančius genus su ligomis.

 

 Laikykite ančiuvius

 

 CRISPR gali būti medicinos ir žemės ūkio transformacijos viršūnėje, tačiau tyrimai jau pasikeitė. Beveik 9000 mokslinių straipsnių savo santraukose paminėjo CRISPR priemones 2024 m., palyginti su 300 2013 m.

 

 Nuo 2012 m. Addgene, ne pelno siekianti DNR reagentų saugykla, išsiuntė daugiau nei 300 000 CRISPR preparatų 5 000 organizacijų maždaug 100 šalių. „Galite tiesiog užsisakyti viską, ko reikia“, – sako Robin Lovell-Badge, vystymosi biologė iš Franciso Cricko instituto Londone. CRISPR RNR gauti taip pat sunku, kaip užsisako picų tyrinėtojai, dirbdami su genų redaktoriais iki nakties.

 

 Tai rimtai sutaupo laiko mokslininkams, besidomintiems fundamentalia biologija, pavyzdžiui, daktarui Lovell-Badge'ui, kurio darbas susijęs su seksualiniu vystymusi. Dešimtajame dešimtmetyje jis atrado, kad Y chromosomos genas, vadinamas SRY, veikė kaip jungiklis, kuris embrionus, kurie pagal nutylėjimą vystosi kaip moterys, pavertė vyriško vystymosi keliu. Tačiau tik pasirodžius CRISPR 2010 m., jis ir kiti suprato, kaip jis iš tikrųjų veikia. Atlikdami išmušamuosius eksperimentus su pelėmis, jie parodė, kad SRY per „stiprintuvo“ geną aktyvuoja kitą geną, vadinamą SOX9, kuris galiausiai skatina sėklidžių vystymąsi.

 

 Suaktyvinkite SOX9 su CRISPR ir „dabar gausite XY patelių“, – sako jis. Kartais tai vyksta natūraliai žmonėms. Kiti mokslininkai neseniai patikrino saujelės žmonių, kuriems pasireiškė priešingos jų chromosominės lyties seksualinės savybės, genomus. Jų mutacijos buvo beveik tokios pačios, kaip ir tų, kurias daktaras Lovell-Badge'as įdėjo į savo pelės embrionus su CRISPR. Tie žmonės dabar žino genetinę savo neįprasto vystymosi priežastį.

 

 Kiekvienas turi savo genetinius variantus, dažniausiai kai viena bazė buvo pakeista kita. Nors visus šiuos variantus galima lengvai rasti nustatant genomo seką, dažnai nežinoma, kurie yra gerybiniai, o kurie žalingi. Tačiau pastaraisiais metais CRISPR paspartino užduotį juos atskirti. Dr. Lovell-Badge'o kolega iš Crick instituto Gregas Findlay naudoja šį įrankį milžiniškai užduočiai spręsti: jis nori suprasti kiekvieną žmogaus genomo variantą, susijusį su liga.

 

 Skaičiuojant tik genų, kurie yra susiję su liga, mutacijas, tai reikštų 30 mln. DNR variantų, sako dr. Findlay. Naudodamas CRISPR ir naujo tipo genų redagavimą, vadinamą pirminiu redagavimu, jis dabar vykdo didžiulius, didelio našumo atrankos eksperimentus, kurių metu tūkstančiai variantų yra išmušami į ląsteles ir analizuojami. „Mes perėjome nuo šių genetikos variantų bandymų po vieną prie didelių telkinių bandymų“, - sako jis. "Dabar mes bandome atlikti eksperimentus, kuriuose yra beveik 100 000 variantų."

 

 Jo rezultatai pradėjo paaiškinti anksčiau gluminančius simptomus. 2024 m. jis paskelbė dokumentą, kuriame nagrinėjami 2 268 VHL, geno, susijusio su navikų slopinimu, variantai ir parodė, kaip konkretūs variantai sukelia skirtingas inkstų vėžio formas ir sunkumo laipsnius. Daugiau tokių CRISPR palaikančių masinių ekranų gali padėti gydytojams patikrinti variantus ir atitinkamai pakoreguoti gydymą.

 

 Tačiau net jei daktaras Findlay gali išplėsti savo eksperimentus, darbas yra tikriausiai per didelis. Yra didelių genomo dalių, kurios yra menkai suprantamos ir kuriose gali būti daug ligas sukeliančių variantų. Ir keli to paties geno – arba skirtingų – variantai gali sąveikauti. „Net jei galėtume išbandyti milijoną variantų, tai vis tiek nė iš tolo neprilygsta 10 mlrd. ar bet ko, kas įmanoma“, – sako jis.

 

 Siekdamas sumažinti apkrovą, jis planuoja pateikti savo duomenis dirbtinio intelekto (AI) modeliui. Jei modelis mokysis visos jau sugeneruotos informacijos, jis tikisi, kad tai leis vis tikslesnes prognozes apie mutacijas, kurių jis dar neišbandė. „Google“ dirbtinio intelekto įmonė „DeepMind“ 2023 m. išleido modelį „Alpha Missense“, kuris atlieka tokio pobūdžio prognozes. Jis buvo lyginamas su eksperimentiniu duomenų rinkiniu, kuriam sugeneruoti prireikė dešimties metų, tačiau dabar įmanomi didžiuliai genų redagavimo ekranai, tokio dydžio duomenų rinkinį galima sukurti per porą mėnesių, sako jis.

 

 Aš esu tas, kuris beldžiasi

 

 Jis nėra vienintelis, kuriam energijos suteikia CRISPR potencialas kurti didelius genetinius ekranus. Silvana Konermann, Kalifornijos pelno nesiekiančio tyrimų instituto „Arc Institute“ direktorė ir viena iš įkūrėjų, sukūrė CRISPR ekraną, naudodama įrankį, galintį sistemingai įjungti genus arba padidinti jų aktyvumą – ką galima pavadinti „numušimu“. Tokios galios reiškia, kad ji gali apversti tradicinį CRISPR ekraną ant galvos. Užuot pradėjusi nuo genetinio varianto ir pažiūrėti, koks yra jo rezultatas, ji gali įvertinti įvykį, pvz., sąlytį su vaistu ar patogenu, ir pamatyti, kurie genai veikia, o kurie neturi įtakos organizmo reakcijai.

 

 Paimkite SARS-CoV-2. 2022 m. Dr Konermann ir jos Arc įkūrėjas Patrickas Hsu sukūrė CRISPR ekraną, kuriame žmogaus plaučių ląstelės turėjo genus, kuriuos išmušė klasikinis CRISPR, arba buvo išmuštas naudojant aktyvinimo įrankį. Tada ląstelės buvo užkrėstos SARS-CoV-2, ir komanda galėjo pasakyti, kurie genai žmogaus ląstelėse padėjo ar trukdė virusui. Virusas stengėsi užkrėsti ląsteles, kuriose buvo aktyvesni už gleivių baltymų gamybą atsakingi genai. Toks genų aktyvumo svyravimas galėtų padėti paaiškinti, kodėl kai kurie žmonės labai nukentėjo nuo koronaviruso, o kiti išgyveno pandemiją nepažeisti. Kai kurie tikriausiai turėjo labai aktyvius gleivių genus.

 

 Kitas atrankos etapas yra nukreipti ne į genus, o į jų produktus. Ląstelė skaito genus ir nukopijuoja juos į RNR grandines. Kai kurios iš šių gijų tampa mRNR, kuri naudojama baltymams gaminti, tačiau dauguma išlieka RNR molekulėmis, veikiančiomis mažai suprantamais būdais. Yra CRISPR sistemų, kurios nukreiptos į RNR, o ne į DNR, įskaitant kai kurias sukurtas Dr. Konermann ir Dr Hsu. Dabar mokslininkai jas naudoja siekdami išsiaiškinti, ką šios molekulės veikia. Daugelis šių keistų RNR buvo susijusios su ligomis, įskaitant psichikos ligas, tokias kaip bipolinis sutrikimas. Jei kas nors pasirodys esąs tinkamas narkotikų taikinys, neabejotinai CRISPRed makakų grupė rytinėje Kinijos pakrantėje bus pasirengusi tai išbandyti." [1]

1. Science superstar. The Economist; London Vol. 454, Iss. 9437,  (Mar 1, 2025): 7, 8.

Using CRIPR in science

"In the late 2010s eight macaque monkeys were born at a laboratory in Shanghai. At first they seemed much like the other infants in the colony, but differences soon became obvious. They were much more active at night than their peers. Their hormones were unusual, too. Melatonin, which typically oscillates with the day-night cycle and aids sleep, was all over the place. Cortisol, a stress hormone, was perpetually high. Then their behaviour took a turn: they sat frozen in corners for long periods of time, fled in fear from their caretakers, and began burying their little heads in their hands—all signs of mental illness.

The root of their malaise was a genetic experiment. When the monkeys were single-celled embryos, scientists had used CRISPR editing tools to silence, or “knock out”, a gene that helps regulate the body’s internal clock. Its disruption is linked to psychiatric conditions, such as bipolar disorder, which are notoriously difficult to study on the genetic and molecular levels. The deeply unpleasant lives of Shanghai macaques are part of a push to understand how genes shape brain disorders and to devise drugs for them.

This could have been done with old technology, but it would have been laborious. Scientists can breed knock-outs using “gene targeting”, a hugely inefficient process that first inserts DNA into stem cells and then into embryos. For mice, it takes a year. CRISPR can do the job in a month. The same is true for adding, or “knocking in”, genetic mutations. Manipulations in both animals and cells have become so quick and easy that scientists can model a host of diseases in the lab, tease apart intricate genetic mechanisms and create huge studies linking genes with diseases.

Hold the anchovies

CRISPR might be on the cusp of transforming medicine and agriculture, but in research things have already changed. Almost 9,000 scientific papers mentioned CRISPR tools in their abstracts in 2024, up from 300 in 2013.

Since 2012 Addgene, a non-profit repository of DNA reagents, has shipped more than 300,000 CRISPR preparations to 5,000 organisations in around 100 countries. “You can just simply order everything you need,” says Robin Lovell-Badge, a developmental biologist at the Francis Crick Institute in London. CRISPR RNA is about as hard to get as the pizzas researchers order when working on gene editors into the night.

That is a serious time-saver for scientists interested in fundamental biology, such as Dr Lovell-Badge, whose work concerns sexual development. In the 1990s he discovered that a gene on the Y chromosome called SRY acted as a switch that turned embryos, which by default develop as female, onto the path of male development. But it was not until the arrival of CRISPR in the 2010s that he and others figured out how it actually works. Through knock-out experiments in mice they showed that SRY, via an “enhancer” gene, activates another gene called SOX9, which ultimately drives the development of the testes.

Knock out that activation of SOX9 with CRISPR and “you now get XY females,” he says. This sometimes happens naturally in humans. Other scientists recently checked the genomes of a handful of people who had developed the opposite sexual characteristics of their chromosomal sex. Their mutations were almost exactly the same as those Dr Lovell-Badge had put into his mouse embryos with CRISPR. Those people now know the genetic cause of their unusual development.

Everyone carries their own genetic variants, usually where one base has been swapped for another. Though all these variants can be easily found with genome sequencing, it is often not known which are benign and which are harmful. But in recent years CRISPR has sped up the task of telling them apart. Greg Findlay, a colleague of Dr Lovell-Badge at the Crick Institute, is using the tool to tackle a gargantuan task: he wants to understand every single variation in the human genome that is associated with disease.

Counting only mutations in genes which are implicated in disease, this would mean knocking in 30m DNA variants, Dr Findlay says. Using CRISPR and a new type of gene editing called prime editing, he now runs massive, high-throughput screening experiments, in which thousands of variants are knocked into cells and analysed. “We’ve gone from testing these variants in genetics one at a time to testing large pools,” he says. “Now we’re trying to do experiments that are close to 100,000 variants.”

His results have begun to explain previously baffling symptoms. In 2024 he published a paper going through 2,268 base-swap variants of VHL, a gene involved with suppressing tumours, and showed how particular variants led to different forms and severities of kidney cancer. More such CRISPR-enabled mass screens might help doctors check for variants and tweak treatment accordingly.

But even if Dr Findlay is able to scale up his experiments, the job is probably too big. There are substantial parts of the genome that are poorly understood, and which may host large numbers of disease-causing variants. And multiple variations in the same gene—or different ones—can interact. “Even if we could test a million variants, it’s still nowhere near the 10bn or whatever that are possible,” he says.

To lessen the load, he plans to feed his data to an artificial intelligence (AI) model. If the model trains on all the information he has already generated, he hopes that it will make increasingly accurate predictions about mutations he has not yet tested. DeepMind, Google’s AI company, put out a model in 2023 called Alpha Missense that does this kind of prediction. It was benchmarked against an experimental data set which took ten years to generate, but with the massive gene-editing screens now possible, a data set of that size could be made in a couple months, he says.

I am the one who knocks

He is not the only one energised by CRISPR’s potential to create big genetic screens. Silvana Konermann, the director and co-founder of the Arc Institute, a non-profit research institute in California, has pioneered a CRISPR screen using a tool that can systematically switch genes on or increase their activity—what one might call “knocking up”. Such powers mean she can flip the traditional CRISPR screen on its head. Rather than start with a genetic variant and see what its outcome is, she can take an event, like exposure to a drug or a pathogen, and see which genes do and do not influence how the body responds.

Take SARS-CoV-2. In 2022 Dr Konermann and her Arc co-founder Patrick Hsu developed a CRISPR screen in which human lung cells had genes either knocked out by classic CRISPR or knocked up using the activation tool. The cells were then infected with SARS-CoV-2, and the team were able to say which genes in the human cells helped or hindered the virus. The virus struggled to infect the cells in which the genes responsible for making mucus proteins were more activated. Such variation in gene activity could help explain why some people suffered greatly from covid while others got through the pandemic unscathed. Some probably had very active mucus genes.

The next stage in screening is to target not the genes, but their products. The cell reads genes and copies them into RNA strands. Some of those strands become mRNA that is used to make proteins, but most remain RNA molecules, acting in ways that remain poorly understood. There are CRISPR systems that target RNA instead of DNA, including some developed by Dr Konermann and Dr Hsu. Scientists are now using them to find out what these molecules do. Many of these strange RNAs have been linked to disease, including psychiatric conditions like bipolar disorder. If one turns out to be a suitable drug target, no doubt a group of CRISPRed macaques on the east coast of China will be ready to test it out." [1]

1. Science superstar. The Economist; London Vol. 454, Iss. 9437,  (Mar 1, 2025): 7, 8.