Technology’s Role in Feeding a Soaring Population Raises This Dilemma
When farmer Terry Wanzek walks out in his fields, he sometimes sees a grove of trees, which reminds him of his grandfather, who planted those trees. Or he looks out over the pond, which deer, ducks and pheasant use for water, and he knows that his grandfather made a decision to drain land and put the pond in that exact spot.
Growing more with fewer resources is becoming increasingly urgent as the Earth's population is expected to hit 9.1 billion by 2050.
"There is a connection that goes beyond running a business and making a profit," says Wanzek, a fourth-generation North Dakota farmer who raises spring wheat, corn, soybeans, barley, dry edible beans and sunflowers. "There is a connection to family, to your ancestors and there is a connection to your posterity and your kids."
Wanzek's corn and soybeans are genetically modified (GM) crops, which means that they have been altered at the DNA level to create desirable traits. This intervention, he says, allows him to start growing earlier and to produce more food per acre.
Growing more with fewer resources is becoming increasingly urgent as the Earth's population is expected to hit 9.1 billion by 2050, with nearly all of the rise coming from developing countries, according to the Food and Agriculture Organization of the United Nations. This population will be urban, which means they'll likely be eating fewer grains and other staple crops, and more vegetables, fruits, meat, dairy, and fish.
Whether those foods will be touched in some way by technology remains a high-stakes question. As for GM foods, the American public is somewhat skeptical: in a recent survey, about one-third of Americans report that they are actively avoiding GMOs or seek out non-GMO labels when shopping and purchasing foods. These consumers fear unsafe food and don't want biotechnologists to tamper with nature. This disconnect—between those who consume food and those who produce it—is only set to intensify as major agricultural companies work to develop further high-tech farming solutions to meet the needs of the growing population.
"I don't think we have a choice going forward. The world isn't getting smaller. We have to come up with a means of using less."
In the future, it may be possible to feed the world. But what if the world doesn't want the food?
A Short History
Genetically modified food is not new. The first such plant (the Flavr Savr tomato) was approved for human consumption and brought to market in 1994, but people didn't like the taste. Today, nine genetically modified food crops are commercially available in the United States (corn, soybean, squash, papaya, alfalfa, sugar beets, canola, potato and apples). Most were modified to increase resistance to disease or pests, or tolerance to a specific herbicide. Such crops have in fact been found to increase yields, with a recent study showing grain yield was up to 24.5 percent higher in genetically engineered corn.
Despite some consumer skepticism, many farmers don't have a problem with GM crops, says Jennie Schmidt, a farmer and registered dietician in Maryland. She says with a laugh that her farm is a "grocery store farm - we grow the ingredients you buy in products at the grocery store." Schmidt's father-in-law, who started the farm, watched the adoption of hybrid corn improve seeds in the 1930s and 1940s.
"It wasn't a difficult leap to see how well these hybrid corn seeds have done over the decades," she says. "So when the GMOs came out, it was a quicker adoption curve, because as farmers they had already been exposed to the first generation and this was just the next step."
Schmidt, for one, is excited about the gene-editing tool CRISPR and other ways biotechnologists can create food like apples or potatoes with a particular enzyme turned off so they don't go brown during oxidation. Other foods in the pipeline include disease-resistant citrus, low-gluten wheat, fungus-resistant bananas, and anti-browning mushrooms.
"We need to not judge our agriculture by yield per acre but nutrition per acre."
"I don't think we have a choice going forward," says Schmidt. "The world isn't getting smaller. We have to come up with a means of using less."
A Different Way Forward?
But others remain convinced that there are better ways to feed the planet. Andrew Kimball, executive director of the Center for Food Safety, a non-profit that promotes organic and sustainable agriculture, says the public has been sold a lie with biotech. "GMO technology is not proven as a food producer," he says. "It's just not being done anywhere at a large scale. Ninety-nine percent of GMOs are corn and soy, and they allow chemical companies to sell more chemicals. But that doesn't increase food or decrease hunger." Instead, Kimball advocates for a pivot from commodity agriculture to farms with crop diversity and animals.
Kimball also suggests a way to use land more appropriately: stop growing so much biofuel. Right now, in the U.S., more than 55 percent of our crop farmland is in corn and soy. About 40 percent of that goes into cars through ethanol, 40 percent is fed to animals and a good bit of the rest goes into high-fructose corn syrup. That leaves only a small amount to feed people, says Kimball. "If you want to feed the world, not just the U.S., you want to make sure to use that land to feed people," he says. "We need to not judge our agriculture by yield per acre but nutrition per acre."
Robert Streiffer, a bioethicist at the University of Wisconsin at Madison, agrees that GMOs haven't really helped alleviate hunger. Glyphosate resistance, one of the traits that is most commonly used in genetically engineered crops, doesn't improve yield or allow crops to be grown in areas where they weren't able to be grown before. "Insect resistance through the insertion of a Bt gene can improve yield, but is mostly used for cotton (which is not a food crop) and corn which goes to feed cattle, a very inefficient method of feeding the hungry, to say the least," he says. Important research is being done in crops such as cassava, which could help relieve global hunger. But in his opinion, these researchers lack the profit potential needed to motivate large private funding sources, so they require more public-sector funding.
"A substantial portion of public opposition is as much about the lack of any perceived benefits for the consumers as it is for outright fear of health or environmental dangers."
"Public opposition to biotech foods is certainly a factor, but I expect this will slowly decline as labels indicating the presence of GE (genetically engineered) ingredients become more common, and as we continue to amass reassuring data on the comparative environmental safety of GE crops," says Streiffer. "A substantial portion of public opposition is as much about the lack of any perceived benefits for the consumers as it is for outright fear of health or environmental dangers."
One sign that the public may be willing to embrace some non-natural foods is the recent interest in cultured meat, which is grown in a lab from animal cells but doesn't require raising or killing animals. A study published last year in PLOS One found that 65 percent of 673 surveyed U.S. individuals would probably or definitely try cultured meat, while only 8.5 percent said they definitely would not. In the future, lab-grown food may become another way to create more food with fewer resources.
Danielle Nierenberg, president of the Food Tank, a nonprofit organization focused on building a global community of safe and healthy food, points to an even more immediate problem: food waste. Globally, about a third of food is thrown out or goes bad before it has a chance to be eaten. She says simply fixing roads and infrastructure in developing countries would go a long way toward ensuring that food reaches the hungry. Focusing on helping small farmers (who grow 70 percent of food around the globe), especially female farmers, would go a long way, she says.
Innovation on the Farm
In addition to good roads, those farmers need fertilizer. Nitrogen-based fertilizers may get a boost in the future from technologies that release nutrients slowly over time, like slow-release medicines based on nanotechnology. In field trials on rice in Sri Lanka, one such nanotech fertilizer increased crop yields by 10 percent, even though it delivered only half the amount of urea compared with traditional fertilizer, according to a study last year.
"I'm not afraid of the food I grow. We live in the same environment, and I feel completely safe."
One startup, the San-Francisco-based Biome Makers, is profiling microbial DNA to give farmers an idea of what their soil needs to better support crops. Joyn Bio, another new startup based in Boston and West Sacramento, is looking to engineer microbes that could reduce farming's reliance on nitrogen fertilizer, which is expensive and harms the environment. (Full disclosure: Joyn Bio and this magazine are funded by the same company, Leaps by Bayer, though leapsmag is editorially independent. Also, Bayer recently acquired Monsanto, the leading producer of genetically engineered seeds and the herbicide Roundup.)
Terry Wanzek, the farmer in North Dakota, says he'd be willing to try any new technology as long as it helps his bottom line – and increases sustainability. "I'm not afraid of the food I grow," he says of his genetically modified produce. "We eat the same food, we live in the same environment, and I feel completely safe."
Only time will tell if people several decades from now feel the same way. But no matter how their food is produced, one thing is certain: those people will need to eat.
Podcast: The Friday Five Weekly Roundup in Health Research
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five:
- Not a fan of breathing in micro plastics? New robot noses could help
- You don't need a near-death experience to get the benefits
- How to tell the difference between good and bad inflammation
- Brain shocks for better memory - don't try this at home (yet)!
- A new way to know if your bum back is getting better
The honorable mention for this week's Friday Five: One activity can increase your longevity even without good genes for living longer.
Schizophrenia is a debilitating mental health condition that affects around 24 million people worldwide. Patients experience hallucinations and delusions when they develop schizophrenia, with experts referring to these new thoughts and behaviors as positive symptoms. They also suffer from negative symptoms in which they lose important functions, suffering from dulled emotions, lack of purpose and social withdrawal.
Currently available drugs can control only a portion of these symptoms but, on August 8th, Karuna Therapeutics announced its completion of a phase 3 clinical trial that found a new drug called KarXT could treat both positive and negative symptoms of schizophrenia. It could mean substantial progress against a problem that has stymied scientists for decades.
A long-standing problem
Since the 1950s, antipsychotics have been used to treat schizophrenia. People who suffer from it are thought to have too much of a brain chemical called dopamine, and antipsychotics work by blocking dopamine receptors in the brain. They can be effective in treating positive symptoms but have little impact on the negative ones, which can be devastating for a patient’s quality of life, making it difficult to maintain employment and have successful relationships. About 30 percent of schizophrenia patients don't actually respond to antipsychotics at all. Current drugs can also have adverse side effects including elevated cholesterol, high blood pressure, diabetes and movements that patients cannot control.
The recent clinical trial heralds a new treatment approach. “We believe it marks an important advancement for patients given its new and completely different mechanism of action from current therapies,” says Andrew Miller, COO of Karuna.
Scientists have been looking to develop alternatives. However, “the field of drug treatment of schizophrenia is currently in the doldrums,” says Peter McKenna, a senior researcher at FIDMAG Research Foundation in Spain which specialises in mental health.
In the 2000s there was a major push to target a brain receptor for a chemical called glutamate. Evidence suggested that this receptor is abnormal in the brains of schizophrenia patients, but attempts to try glutamate failed in clinical trials.
After that, many pharmaceutical companies dropped out of the race for a more useful treatment. But some companies continued to search, such as Karuna Therapeutics, led by founder and Chief Operating Officer Andrew Miller and CEO Steve Paul. The recent clinical trial suggests their persistence has led to an important breakthrough with their drug, KarXT. “We believe it marks an important advancement for patients given its new and completely different mechanism of action from current therapies,” Miller says.
How it works
Neurotransmitters are chemical messengers that pass signals between neurons. To work effectively, neurotransmitters need a receptor to bind to. A neurotransmitter called acetylcholine seems to be especially important in schizophrenia. It interacts with sites called muscarinic receptors, which are involved in the network of nerves that calm your body after a stressful event. Post mortem studies in people with schizophrenia have shown that two muscarinic receptors in the brain, the M1 and M4 receptors, are activated at unusually low levels because they don’t receive enough signals from acetylcholine.
The M4 receptor appears to play a role in psychosis. The M1 receptor is also associated with psychosis but is primarily thought to be involved in cognition. KarXT, taken orally, works by activating both of these receptors to signal properly. It is this twofold action that seems to explain its effectiveness. “[The drug’s] design enables the preferential stimulation of these muscarinic receptors in the brain,” Miller says.
How it developed
It all started in the early 1990s when Paul was at pharmaceutical company Eli Lilly. He discovered that Xanomeline, the drug they were testing on Alzheimer's patients, had antipsychotic effects. It worked by stimulating M1 and M4 receptors, so he and his colleagues decided to test Xanomeline on schizophrenia patients, supported by research on the connection between muscarinic receptors and psychosis. They found that Xanomeline reduced both positive and negative symptoms.
Unfortunately, it also caused significant side effects. The problem was that stimulating the M1 and M4 receptors in the brain also stimulated muscarinic receptors in the body that led to severe vomiting, diarrhea and even the temporary loss of consciousness.
In the end, Eli Lilly discontinued the clinical trials for the drug, but Miller set up Karuna Therapeutics to develop a solution. “I was determined to find a way to harness the therapeutic benefit demonstrated in studies of Xanomeline, while eliminating side effects that limited its development,” Miller says.
He analysed over 7,000 possible ways of mixing Xanomeline with other agents before settling on KarXT. It combines Xanomeline with a drug called Trospium Chloride, which blocks muscarinic receptors in the body – taking care of the side effects such as vomiting – but leaves them unblocked in the brain. Paul was so excited by Miller’s progress that he joined Karuna after leaving Eli Lilly and founding two previous startups.
“It's a very important approach,” says Rick Adams, Future Leaders Fellow in the Institute of Cognitive Neuroscience and Centre for Medical Image Computing at University College London. “We are in desperate need of alternative drug targets and this target is one of the best. There are other alternative targets, but not many are as close to being successful as the muscarinic receptor drug.”
Clinical Trial
Following a successful phase 2 clinical trial in 2019, the most recent trial involved 126 patients who were given KarXT, and 126 who were given a placebo. Compared to the placebo, patients taking KarXT had a significant 9.6 point reduction in the positive and negative syndrome scale (PANSS), the standard for rating schizophrenic symptoms.
KarXT also led to statistically significant declines in positive and negative symptoms compared to the placebo. “The results suggest that KarXT could be a potentially game-changing option in the management of both positive and negative symptoms of schizophrenia,” Miller says.
Robert McCutcheon, a psychiatrist and neuroscientist at Oxford University, is optimistic about the side effects but highlights the need for more safety trials.
McKenna, the researcher at FIDMAG Foundation, agrees about the drug’s potential. “The new [phase 3] study is positive,” he says. “It is reassuring that one is not dealing with a drug that works in one trial and then inexplicably fails in the next one.”
Robert McCutcheon, a psychiatrist and neuroscientist at Oxford University, said the drug is an unprecedented step forward. “KarXT is one of the first drugs with a novel mechanism of action to show promise in clinical trials.”
Even though the drug blocks muscarine receptors in the body, some patients still suffered from adverse side effects like vomiting, dizziness and diarrhea. But in general, these effects were mild to moderate, especially compared to dopamine-blocking antipsychotics or Xanomeline on its own.
McCutcheon is optimistic about the side effects but highlights the need for more safety trials. “The trial results suggest that gastrointestinal side effects appear to be manageable,” he says. “We know, however, from previous antipsychotic drugs that the full picture regarding the extent of side effects can sometimes take longer to become apparent to clinicians and patients. Careful ongoing assessment during a longer period of treatment will therefore be important.”
The Future
The team is currently conducting three other trials to evaluate the efficacy and long-term safety of KarXT. Their goal is to receive FDA approval next year.
Karuna is also conducting trials to evaluate the effectiveness of KarXT in treating psychosis in patients suffering from Alzheimer’s.
The big hope is that they will soon be able to provide a radically different drug to help many patients with schizophrenia. “We are another step closer to potentially providing the first new class of medicine in more than 50 years to the millions of people worldwide living with schizophrenia,” says Miller.