[Editor's Note: This essay is in response to our current Big Question series: "How can the religious and scientific communities work together to foster a culture that is equipped to face humanity's biggest challenges?"]
In May 2015, Pope Francis issued an encyclical with the subtitle "On Care for Our Common Home." The letter addressed various environmental issues, such as pollution and climate change, and it reminded all of us that we are to steward the Earth, not plunder it.
Without question, biotechnology has saved the lives of millions – perhaps billions – of people.
The Pope's missive demonstrates that he is both theologically sound and scientifically literate, a very rare combination. That is why he should now author an encyclical urging the world to embrace the life-giving promise of biotechnology.
Without question, biotechnology has saved the lives of millions – perhaps billions – of people. Arguably, vaccines were the most important invention in the history of mankind. It is thought that, in the 20th century alone, at least 300 million people were killed by smallpox. Today, the number is zero, thanks to vaccination. Other killers, such as measles, diphtheria, meningitis, and diarrhea, are kept at bay because of vaccines.
Biotechnology has also saved the lives of diabetics. At one time, insulin was extracted from pig pancreases, and there were fears that we would run out of it. Then, in the 1970s, crucial advances in biotechnology allowed for the gene that encodes human insulin to be expressed in bacteria. Today, diabetics can get extremely pure insulin thanks to this feat of genetic modification.
Likewise, genetic modification has improved the environment and the lives of farmers all over the world, none more so than those living in developing countries. According to a meta-analysis published in PLoS ONE, GMOs have "reduced chemical pesticide use by 37%, increased crop yields by 22%, and increased farmer profits by 68%."
Even better, GMOs also could help improve the lives of non-farmers. In poor parts of the world, malnutrition is still extremely common. People whose diets consist mostly of rice, for example, often suffer from vitamin A deficiency, which can lead to blindness. Golden Rice, which was genetically modified to contain a vitamin A precursor, was created and given away for free in an act of humanitarianism. Other researchers have created a genetically modified cassava to help combat iron and zinc deficiencies among children in Africa.
Despite these groundbreaking advances, the public is turning against biotechnology.
Biotechnology has also helped women with mitochondrial disease bear healthy children. Children inherit their mitochondria, the powerhouses of our cells, solely from their mothers. Mitochondrial defects can have devastating health consequences. Using what is colloquially called the "three-parent embryo technique," a healthy woman donates an egg. The nucleus of that egg is removed, and that of the mother-to-be is put in its place. Then, the egg is fertilized using conventional in vitro fertilization. In April 2016, the world's first baby was born using this technique.
Yet, despite these groundbreaking advances, the public is turning against biotechnology. Across America and Europe, anti-vaccine activists have helped usher in a resurgence of entirely preventable diseases, such as measles. Anti-GMO activists have blocked the implementation of Golden Rice. And other activists decry reproductive technology as "playing God."
Nonsense. These technologies improve overall welfare and save lives. Those laudable goals are shared by all the world's major religions as part of their efforts to improve the human condition. That is why it is vitally important, if science is to succeed in eradicating illness, that it gets a full-throated endorsement from powerful religious leaders.
In his 2015 encyclical, Pope Francis wrote:
Any technical solution which science claims to offer will be powerless to solve the serious problems of our world if humanity loses its compass, if we lose sight of the great motivations which make it possible for us to live in harmony, to make sacrifices and to treat others well.
He is correct. Indeed, when people are protesting life-saving vaccines, we have lost not only our moral compass but our intellect, too.
Imagine the impact he could have if Pope Francis issued an encyclical titled "On Protecting Our Most Vulnerable." He could explain that some children, stricken with cancer or suffering from an immunological disease, are unable to receive vaccines. Therefore, we all have a moral duty to be vaccinated in order to protect them through herd immunity.
Or imagine the potential impact of an encyclical titled "On Feeding the World," in which the Pope explained that rich countries have an obligation to poorer ones to feed them by all means necessary, including the use of biotechnology. If Muslim, Buddhist, and Hindu scholars throughout Asia and Africa also embraced the message, its impact could be multiplied.
In order to be successful, science needs religion; in order to be practical, religion needs science.
In order to be successful, science needs religion; in order to be practical, religion needs science.
Unfortunately, in discussions of the relationship between science and religion, we too often focus on the few areas in which they conflict. But this misses a great opportunity. By combining technological advances with moral authority, science and religion can work together to save the world.
In November 2020, messenger RNA catapulted into the public consciousness when the first COVID-19 vaccines were authorized for emergency use. Around the same time, an equally groundbreaking yet relatively unheralded application of mRNA technology was taking place at a London hospital.
Over the past two decades, there's been increasing interest in harnessing mRNA — molecules present in all of our cells that act like digital tape recorders, copying instructions from DNA in the cell nucleus and carrying them to the protein-making structures — to create a whole new class of therapeutics.
Scientists realized that artificial mRNA, designed in the lab, could be used to instruct our cells to produce certain antibodies, turning our bodies into vaccine-making factories, or to recognize and attack tumors. More recently, researchers recognized that mRNA could also be used to make another groundbreaking technology far more accessible to more patients: gene editing. The gene-editing tool CRISPR has generated plenty of hype for its potential to cure inherited diseases. But delivering CRISPR to the body is complicated and costly.
"Most gene editing involves taking cells out of the patient, treating them and then giving them back, which is an extremely expensive process," explains Drew Weissman, professor of medicine at the University of Pennsylvania, who was involved in developing the mRNA technology behind the COVID-19 vaccines.
But last November, a Massachusetts-based biotech company called Intellia Therapeutics showed it was possible to use mRNA to make the CRISPR system inside the body, eliminating the need to extract cells out of the body and edit them in a lab. Just as mRNA can instruct our cells to produce antibodies against a viral infection, it can also teach them to produce the two molecular components that make up CRISPR — a guide molecule and a cutting protein — to snip out a problem gene.
"The pandemic has really shown that not only are mRNA approaches viable, they could in certain circumstances be vastly superior to more traditional technologies."
In Intellia's London-based clinical trial, the company applied this for the first time in a patient with a rare inherited liver disease known as hereditary transthyretin amyloidosis with polyneuropathy. The disease causes a toxic protein to build up in a person's organs and is typically fatal. In a company press release, Intellia's president and CEO John Leonard swiftly declared that its mRNA-based CRISPR therapy could usher in a "new era of potential genome editing cures."
Weissman predicts that turning CRISPR into an affordable therapy will become the next major frontier for mRNA over the coming decade. His lab is currently working on an mRNA-based CRISPR treatment for sickle cell disease. More than 300,000 babies are born with sickle cell every year, mainly in lower income nations.
"There is a FDA-approved cure, but it involves taking the bone marrow out of the person, and then giving it back which is prohibitively expensive," he says. It also requires a patient to have a matched bone marrow done. "We give an intravenous injection of mRNA lipid nanoparticles that target CRISPR to the bone marrow stem cells in the patient, which is easy, and much less expensive."
Meanwhile, the overwhelming success of the COVID-19 vaccines has focused attention on other ways of using mRNA to bolster the immune system against threats ranging from other infectious diseases to cancer.
The practicality of mRNA vaccines – relatively small quantities are required to induce an antibody response – coupled with their adaptable design, mean companies like Moderna are now targeting pathogens like Zika, chikungunya and cytomegalovirus, or CMV, which previously considered commercially unviable for vaccine developers. This is because outbreaks have been relatively sporadic, and these viruses mainly affect people in low-income nations who can't afford to pay premium prices for a vaccine. But mRNA technology means that jabs could be produced on a flexible basis, when required, at relatively low cost.
Other scientists suggest that mRNA could even provide a means of developing a universal influenza vaccine, a goal that's long been the Holy Grail for vaccinologists around the world.
"The mRNA technology allows you to pick out bits of the virus that you want to induce immunity to," says Michael Mulqueen, vice president of business development at eTheRNA, a Belgium-based biotech that's developing mRNA-based vaccines for malaria and HIV, as well as various forms of cancer. "This means you can get the immune system primed to the bits of the virus that don't vary so much between strains. So you could actually have a single vaccine that protects against a whole raft of different variants of the same virus, offering more universal coverage."
Before mRNA became synonymous with vaccines, its biggest potential was for cancer treatments. BioNTech, the German biotech company that collaborated with Pfizer to develop the first authorized COVID-19 vaccine, was initially founded to utilize mRNA for personalized cancer treatments, and the company remains interested in cancers ranging from melanoma to breast cancer.
One of the major hurdles in treating cancer has been the fact that tumors can look very different from one person to the next. It's why conventional approaches, such as chemotherapy or radiation, don't work for every patient. But weaponizing mRNA against cancer primes the immune cells with the tumor's specific genetic sequence, training the patient's body to attack their own unique type of cancer.
"It means you're able to think about personalizing cancer treatments down to specific subgroups of patients," says Mulqueen. "For example, eTheRNA are developing a renal cell carcinoma treatment which will be targeted at around 20% of these patients, who have specific tumor types. We're hoping to take that to human trials next year, but the challenge is trying to identify the right patients for the treatment at an early stage."
Repairing Damaged mRNA
While hopes are high that mRNA could usher in new cancer treatments and make CRISPR more accessible, a growing number of companies are also exploring an alternative to gene editing, known as RNA editing.
In genetic disorders, the mRNA in certain cells is impaired due to a rogue gene defect, and so the body ceases to produce a particular vital protein. Instead of permanently deleting the problem gene with CRISPR, the idea behind RNA editing is to inject small pieces of synthetic mRNA to repair the existing mRNA. Scientists think this approach will allow normal protein production to resume.
Over the past few years, this approach has gathered momentum, as some researchers have recognized that it holds certain key advantages over CRISPR. Companies from Belgium to Japan are now looking at RNA editing to treat all kinds of disorders, from Huntingdon's disease, to amyotrophic lateral sclerosis, or ALS, and certain types of cancer.
"With RNA editing, you don't need to make any changes to the DNA," explains Daniel de Boer, CEO of Dutch biotech ProQR, which is looking to treat rare genetic disorders that cause blindness. "Changes to the DNA are permanent, so if something goes wrong, that may not be desirable. With RNA editing, it's a temporary change, so we dose patients with our drugs once or twice a year."
Last month, ProQR reported a landmark case study, in which a patient with a rare form of blindness called Leber congenital amaurosis, which affects the retina at the back of the eye, recovered vision after three months of treatment.
"We have seen that this RNA therapy restores vision in people that were completely blind for a year or so," says de Boer. "They were able to see again, to read again. We think there are a large number of other genetic diseases we could go after with this technology. There are thousands of different mutations that can lead to blindness, and we think this technology can target approximately 25% of them."
Ultimately, there's likely to be a role for both RNA editing and CRISPR, depending on the disease. "I think CRISPR is ideally suited for illnesses where you would like to permanently correct a genetic defect," says Joshua Rosenthal of the Marine Biology Laboratory in Chicago. "Whereas RNA editing could be used to treat things like pain, where you might want to reset a neural circuit temporarily over a shorter period of time."
Much of this research has been accelerated by the COVID-19 pandemic, which has played a major role in bringing mRNA to the forefront of people's minds as a therapeutic.
"The pandemic has really shown that not only are mRNA approaches viable, they could in certain circumstances be vastly superior to more traditional technologies," says Mulqueen. "In the future, I would not be surprised if many of the top pharma products are mRNA derived."
"Making Sense of Science" is a monthly podcast that features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This episode is hosted by science and biotech journalist Emily Mullin, summer editor of the award-winning science outlet Leaps.org.