The media loves to hype concerns about artificial intelligence: What if machines become super-intelligent and self-aware? How will humanity compete and survive? But artificial intelligence today is a far cry from a robot takeover. "AI" is a catch-all term that often refers to machine training or machine learning: There is an abundance of data, vastly more than the human mind can assimilate, being tagged, captured and stored. This systematic data processing requires methodologies that can put it in usable form and formats. While these new developments stoke fear in some corners, the ability to predict outcomes is generally seen as a good thing, as it can mitigate risks and even save lives.
We, collectively, want AI even though it is seldom expressed this way.
The prospects and attempts toward artificial intelligence has been with us for decades. Only recently have the underlying technologies and infrastructure--including computer processing, storage, networking speed and advanced software platforms--become omnipresent. These technological advances enabled the implementation of data mining concepts and the subsequent advantages that were not feasible just a decade ago.
AI is fantastical by vision, evolutionary by experience, and disruptive upon reflection. In the world of health care, AI is already transforming research and clinical practice. We, collectively, want AI even though it is seldom expressed this way. What we, the patient population, patient advocates and caregivers, agree on and want is: (1) timely, precise and inexpensive diagnoses of our ailments, injuries and disorders; (2) timely, personalized, highly effective and efficient courses of therapies; and (3) expedited recovery with minimum deficits, complications and recurrence.
"Artificial intelligence and machine learning will impact healthcare as profoundly as the discovery of the microscope."
Implicitly, we all are saying that we want our healthcare systems and clinicians to accomplish truly inhuman feats: to incorporate all sources of structured data (such as published statistics and reports) and unstructured data (including news articles, conversational analysis by care givers, nuances of similar cases, talks at professional societies); to analyze the data sourced and uncover patterns, reveal side effects, define probable success and outcomes; and to present the best personalized course of treatment for the patient that addresses the ailment and mitigates associated risks. It is hard to argue against any of this.
In a recent published interview, Keith J. Dreyer, executive director of the Massachusetts General Hospital and Brigham and Women's Hospital Center for Clinical Data Science, says that "artificial intelligence and machine learning will impact healthcare as profoundly as the discovery of the microscope."
But as AI helps physicians in profound ways, like detecting subtle lesions on scans or distinguishing the symptoms of a stroke from a brain tumor, we humans can't get too complacent. Evolving AI platforms will provide more sophisticated sets of "tools" to address both mundane and complex medical challenges, albeit with humans very much in the mix and routinely at the helm.
Humans do not appear endangered to be replaced anytime soon.
Human beings are capable of a level of nuance and contextual understanding of complex medical scenarios and, consequently, do not appear endangered to be replaced anytime soon. These platforms will do some heavy lifting for sure and provide considerable assistance across the healthcare industry. But human involvement is crucial, as we are best at adaptive learning, cognition, ensuring accuracy of the data, and continually providing feedback to improve the machine learning components of the AI platforms that the health industry will increasingly rely upon.
The human/machine interface is not binary; there is no line in the sand. It is fuzzy and evolutionary, a synchronicity that we all will surely witness and experience. In the future, it may be possible that all recorded knowledge, including genetic, genomic and laboratory data, from structured and unstructured sources, can be at the fingertips of your clinician, and then factored into diagnosing your condition and prescribing your course of treatment. This is precision and personalized medicine on a grand scale applied at the micro level--you!
But none of this will diminish the importance of doctors, nurses and all assortment of care providers. Though they all will undoubtedly become more effective with such awesome AI assistance, their job will always be to heal you with compassion, wisdom, and kindness, for the essence of humanity cannot be automated.
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.