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.
Did Anton the AI find a new treatment for a deadly cancer?
Bile duct cancer is a rare and aggressive form of cancer that is often difficult to diagnose. Patients with advanced forms of the disease have an average life expectancy of less than two years.
Many patients who get cancer in their bile ducts – the tubes that carry digestive fluid from the liver to the small intestine – have mutations in the protein FGFR2, which leads cells to grow uncontrollably. One treatment option is chemotherapy, but it’s toxic to both cancer cells and healthy cells, failing to distinguish between the two. Increasingly, cancer researchers are focusing on biomarker directed therapy, or making drugs that target a particular molecule that causes the disease – FGFR2, in the case of bile duct cancer.
A problem is that in targeting FGFR2, these drugs inadvertently inhibit the FGFR1 protein, which looks almost identical. This causes elevated phosphate levels, which is a sign of kidney damage, so doses are often limited to prevent complications.
In recent years, though, a company called Relay has taken a unique approach to picking out FGFR2, using a powerful supercomputer to simulate how proteins move and change shape. The team, leveraging this AI capability, discovered that FGFR2 and FGFR1 move differently, which enabled them to create a more precise drug.
Preliminary studies have shown robust activity of this drug, called RLY-4008, in FGFR2 altered tumors, especially in bile duct cancer. The drug did not inhibit FGFR1 or cause significant side effects. “RLY-4008 is a prime example of a precision oncology therapeutic with its highly selective and potent targeting of FGFR2 genetic alterations and resistance mutations,” says Lipika Goyal, assistant professor of medicine at Harvard Medical School. She is a principal investigator of Relay’s phase 1-2 clinical trial.
Boosts from AI and a billionaire
Traditional drug design has been very much a case of trial and error, as scientists investigate many molecules to see which ones bind to the intended target and bind less to other targets.
“It’s being done almost blindly, without really being guided by structure, so it fails very often,” says Olivier Elemento, associate director of the Institute for Computational Biomedicine at Cornell. “The issue is that they are not sampling enough molecules to cover some of the chemical space that would be specific to the target of interest and not specific to others.”
Relay’s unique hardware and software allow simulations that could never be achieved through traditional experiments, Elemento says.
Some scientists have tried to use X-rays of crystallized proteins to look at the structure of proteins and design better drugs. But they have failed to account for an important factor: proteins are moving and constantly folding into different shapes.
David Shaw, a hedge fund billionaire, wanted to help improve drug discovery and understood that a key obstacle was that computer models of molecular dynamics were limited; they simulated motion for less than 10 millionths of a second.
In 2001, Shaw set up his own research facility, D.E. Shaw Research, to create a supercomputer that would be specifically designed to simulate protein motion. Seven years later, he succeeded in firing up a supercomputer that can now conduct high speed simulations roughly 100 times faster than others. Called Anton, it has special computer chips to enable this speed, and its software is powered by AI to conduct many simulations.
After creating the supercomputer, Shaw teamed up with leading scientists who were interested in molecular motion, and they founded Relay Therapeutics.
Elemento believes that Relay’s approach is highly beneficial in designing a better drug for bile duct cancer. “Relay Therapeutics has a cutting-edge approach for molecular dynamics that I don’t believe any other companies have, at least not as advanced.” Relay’s unique hardware and software allow simulations that could never be achieved through traditional experiments, Elemento says.
How it works
Relay used both experimental and computational approaches to design RLY-4008. The team started out by taking X-rays of crystallized versions of both their intended target, FGFR2, and the almost identical FGFR1. This enabled them to get a 3D snapshot of each of their structures. They then fed the X-rays into the Anton supercomputer to simulate how the proteins were likely to move.
Anton’s simulations showed that the FGFR1 protein had a flap that moved more frequently than FGFR2. Based on this distinct motion, the team tried to design a compound that would recognize this flap shifting around and bind to FGFR2 while steering away from its more active lookalike.
For that, they went back Anton, using the supercomputer to simulate the behavior of thousands of potential molecules for over a year, looking at what made a particular molecule selective to the target versus another molecule that wasn’t. These insights led them to determine the best compounds to make and test in the lab and, ultimately, they found that RLY-4008 was the most effective.
Promising results so far
Relay began phase 1-2 trials in 2020 and will continue until 2024. Preliminary results showed that, in the 17 patients taking a 70 mg dose of RLY-4008, the drug worked to shrink tumors in 88 percent of patients. This was a significant increase compared to other FGFR inhibitors. For instance, Futibatinib, which recently got FDA approval, had a response rate of only 42 percent.
Across all dose levels, RLY-4008 shrank tumors by 63 percent in 38 patients. In more good news, the drug didn’t elevate their phosphate levels, which suggests that it could be taken without increasing patients’ risk for kidney disease.
“Objectively, this is pretty remarkable,” says Elemento. “In a small patient study, you have a molecule that is able to shrink tumors in such a high fraction of patients. It is unusual to see such good results in a phase 1-2 trial.”
A simulated future
The research team is continuing to use molecular dynamic simulations to develop other new drug, such as one that is being studied in patients with solid tumors and breast cancer.
As for their bile duct cancer drug, RLY-4008, Relay plans by 2024 to have tested it in around 440 patients. “The mature results of the phase 1-2 trial are highly anticipated,” says Goyal, the principal investigator of the trial.
Sameek Roychowdhury, an oncologist and associate professor of internal medicine at Ohio State University, highlights the need for caution. “This has early signs of benefit, but we will look forward to seeing longer term results for benefit and side effect profiles. We need to think a few more steps ahead - these treatments are like the ’Whack-a-Mole game’ where cancer finds a way to become resistant to each subsequent drug.”
“I think the issue is going to be how durable are the responses to the drug and what are the mechanisms of resistance,” says Raymond Wadlow, an oncologist at the Inova Medical Group who specializes in gastrointestinal and haematological cancer. “But the results look promising. It is a much more selective inhibitor of the FGFR protein and less toxic. It’s been an exciting development.”
The Friday Five: How to exercise for cancer prevention
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.
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Here are the promising studies covered in this week's Friday Five:
- How to exercise for cancer prevention
- A device that brings relief to back pain
- Ingredients for reducing Alzheimer's risk
- Is the world's oldest disease the fountain of youth?
- Scared of crossing bridges? Your phone can help