Imagine if you could eat potato chips to help you lose weight or drink a medicine-infused tea to treat cancer or ease chronic pain. Imagine if you could consume cheaper, environmentally friendly medicine through edible plants that have been genetically engineered as “natural drugs” grown in your own back yard. As farfetched as this sounds, “plant cures” are the key to world-first research by a team of scientists at the University of Queensland (UQ), led by Professor David Craik. The main goal for his team of 35 scientists was to address one of the world’s greatest health challenges — to find a way to make medicines safer and more effective than chemically made drugs. “We’re engineering plants into super-efficient producers of next-generation medicines,” Professor Craik said.
Their research has attracted worldwide interest and led to collaborations with the US, UK, China, Sweden and Austria. When it comes to battling obesity, Professor Craik said he had proved his team could make molecules that act on a receptor in the brain that affects appetite, controls the desire for food, and therefore can cause weight loss. “We have shown our molecules are very potent – a thousand millionth of a gram is enough to stimulate that receptor to effectively turn it off, so our appetite would be suppressed,” he said. “So we want to put that molecule into, say, potatoes, so that effectively you can have your french fries and not worry about the consequences.”Professor Craik said you would feel “full” after a few chips because your brain would tell you you were no longer hungry.
Cone snail venom and chronic pain
He said the use of plants to ease chronic pain was also showing promise. After discovering “mini proteins”, Professor Craik examined the structures of many animal toxins, including conotoxins from cone snail venoms. “With pain, we actually discovered a molecule from a Queensland cone snail, which is a marine snail that injects venom into passing fish, and it turns out that is a very potent pain killer,” Professor Craik said. “We have now engineered that pain killer to be put into the native Australian tobacco plant so that we can essentially grow that pain-killing medicine in that plant. “The molecule from a Queensland cone snail is about 150 times more potent than morphine. “And one of our goals is to put that into plants, perhaps an edible plant so people could have their pain-killing medicine as part of their diet. “When one thinks of the term tobacco, visions of smoke and lung cancer come to mind, but we use these plants to produce medicines with the potential to save lives.”
The team with UQ’s Institute for Molecular Bioscience also has its sights set on using genetically engineered tomato plants as a potential drug to treat the debilitating chronic disease of multiple sclerosis (MS), which impacts the nervous system. “One of the cyclic peptides [mini proteins] we work on is going to clinical trials in Sweden this year as a potential treatment for the disease,” Professor Craik said. “So we thought wouldn’t it be neat if people could be having a salad with these special tomatoes in it and relieve some of the symptoms of their MS at the same time.”
‘The lab rat of the plant world’
Professor Craik’s lab has also been putting anti-cancer drugs into sunflowers and soybean plants, while other pain relief drugs have been injected into a common, fast-growing weed in the cabbage family called Arabidopsis Thaliana. “It is sort of like the lab rat of the plant world,” he said. “It can be turned around very quickly, so we use that for all of our model experiments to see if we can put genes in medicines into that plant, first of all. “If we get that working, that’s when we can go to larger plants with confidence; crop plants, like tobacco. We are also using petunias and even peanuts.”
The research is complex and began with a light bulb moment for Professor Craik when he studied how women in the Congo were drinking a tea to ease pain during childbirth in the 1970s. “We found that the active ingredient in an African medicine was actually a peptide with a weird and circular structure that made them stable,” he said. “The women in Africa were making a tea from this plant that contained a peptide [by] boiling the tea and ingesting it. “The fact that a peptide could survive boiling and ingestion was a real eye-opening moment as most peptides can’t do that.”
Injecting plants one leaf at a time
Professor Craik said his team had travelled around the world searching for plants containing active molecules that are brought back to the lab and tested.
Walking around the lab, molecular biologists are seen injecting between 20 or 30 plants with bacterium that have been engineered to encode the peptides.
Scientist Max Harding injected a tobacco plant, one infection per leaf, before putting the plant back into the hot house to “re grow” as a “plant drug”.”We understand how well nature’s producing these molecules naturally so what if we can re-engineer them to be anti-cancer drugs, anti-obesity drugs or pain killers?” Mr Harding said. “Why not use plants as bio-factories and produce them in large amounts and that way we can produce next generation pharmaceuticals without using toxic chemicals for the production process.” He said plant-grown drugs would be more accessible. “Instead of needing expensive chemical factories and complicated transport chains to make and distribute medicines, we could have plants making these medicines,” Mr Harding said. “All you need is some sunlight, some water and a bit or land and we can make sustainable medicines that will be more accessible safer and hopefully cheaper for patients.”
While the molecules they were working on have shown success in animal studies, clinical trials were still at least five years away. Dr Annie Kan, who has a PhD in medicinal chemistry and is also part of Professor Craik’s research team, said she hoped their research had the potential to create a revolution in medicine, particularly in developing countries where there was a need for more affordable drugs. “Because plants have already learnt to make the structures for millions of years, we sort of adjust it a little, put it back into the plant then they will become a lab essentially,” Dr Kan said. “To think that maybe one day our research will be able help people have a better life, that is what inspires me. “So instead of having to go to a hospital and have an injection of your medicine, we are hoping you can, say for example eat a sunflower seed, or brew a tea or eat re-engineered pieces of potato to cure the disease.”
A possible alternative to opioid drugs
Pain Australia CEO Carol Bennett said with 3.4 million Australians impacted by chronic pain, she cannot wait to hear the results of the eventual clinical trials. “The mainstay of pain management has been opioid medication for some time and with increasing dependence and harm, its use for managing chronic pain has become more restricted,” she said. “Natural treatments that show promise for managing pain in its earliest stages before it progresses to chronic pain need to be funded and supported. “Professor Craik’s research is showing some promise for people living with chronic pain and we would be keen to see further results from his research.” Dietitian Kate DiPrima said it was exciting times when science and nature came together to produce foods that heal. “We all know turmeric [anti-inflammatory] and ginger [anti-nausea] work but modifying a protein to safely act on brain receptors to suppress the urge to overeat has to be a good thing,” she said. “I don’t think it means you can eat whatever you like — it will just help stop the overeating, which I see all the time in my patients. “Also, many medications available have side effects like jittery and sleepless nights — and surgically removing part of the stomach — are all very extreme.”
What do drug companies think?
The team said pharmaceutical companies had surprisingly expressed interest in the “bio-pill” research. “A lot of people would say to me the pharmaceutical industry will hate me because we are taking away their industry,” Professor Craik said. “But in fact, they actually like this because this is giving them a way to produce some of these peptide-based medicines inexpensively. “They are all about trying to get products out there as cheaply as possible.”