Leading direct-to-consumer (DTC) genetic testing companies are continuously unveiling novel ways to leverage their vast stores of genetic data.
"23andMe will tell you what diseases you have and then sell you the drugs to treat them."
As reported last week, 23andMe's latest concept is to develop and license new drugs using the data of consumers who have opted in to let their information be used for research. To date, over 10 million people have used the service and around 80 percent have opted in, making its database one of the largest in the world.
Culture researcher Dr. Julia Creet is one of the foremost experts on the DTC genetic testing industry, and in her forthcoming book, The Genealogical Sublime, she bluntly examines whether such companies' motives and interests are in sync with those of consumers.
Leapsmag caught up with Creet about the latest news and the wider industry's implications for health and privacy.
23andMe has just announced that it plans to license a newly developed anti-inflammatory drug, the first one created using its customers' genetic data, to Almirall, a pharma company in Spain. What's your take?
I think this development is the next step in the evolution of the company and its "double-sided" marketing model. In the past, as it enticed customers to give it their DNA, it sold the results and the medical information divulged by customers to other drug companies. Now it is positioning itself to reap the profits of a new model by developing treatments itself.
Given that there are many anti-inflammatory drugs on the market already, whatever Almirall produces might not have much of an impact. We might see this canny move as a "proof of concept," that 23andMe has learned how to "leverage" its genetic data without having to sell them to a third party. In a way, the privacy provisions will be much less complicated, and the company stands to attract investment as it turns itself into [a pseudo pharmaceutical company], a "pharma-psuedocal" company.
Emily Drabant Conley, the president of business development, has said that 23andMe is pursuing other drug compounds and may conduct their own clinical trials rather than licensing them out to their existing research partners. The end goal, it seems, is to make direct-to-consumer DNA testing to drug production and sales back to that same consumer base a seamless and lucrative circle. You have to admit it's a brilliant business model. 23andMe will tell you what diseases you have and then sell you the drugs to treat them.
In your new book, you describe how DTC genetic testing companies have capitalized on our innate human desire to connect with or ancestors and each other. I quote you: "This industry has taken that potent, spiritual, all-too-human need to belong... and monetized it in a particularly exploitative way." But others argue that DTC genetic testing companies are merely providing a service in exchange for fair-market compensation. So where does exploitation come into the picture?
Yes, the industry provides a fee for service, but that's only part of the story. The rest of the story reveals a pernicious industry that hides its business model behind the larger science project of health and heredity. All of the major testing companies play on the idea of "lack," that we can't know who we are unless we buy information about ourselves. When you really think about it, "Who do you think you are?" is a pernicious question that suggests that we don't or can't know who we or to whom we are related without advanced data searches and testing. This existential question used to be a philosophical question; now the answers are provided by databases that acquire more valuable information than they provide in the exchange.
"It's a brilliant business model that exploits consumer naiveté."
As you've said before, consumers are actually paying to be the product because the companies are likely to profit more from selling their genetic data. Could you elaborate?
The largest databases, AncestryDNA and 23andMe, have signed lucrative agreements with biotech companies that pay them for the de-identified data of their customers. What's so valuable is the DNA combined with the family relationships. Consumers provide the family relationships and the companies link and extrapolate the results to larger and larger family trees. Combined with the genetic markers for certain diseases, or increased susceptibility to certain diseases, these databases are very valuable for biotech research.
None of that value will ever be returned to consumers except in the form of for-profit drugs. Ancestry, in particular, has removed all information about its "research partners" from its website, making it very difficult to see how it is profiting from its third-party sales. 23andMe is more open about its "two-sided business model," but encourages consumers to donate their information to science. It's a brilliant business model that exploits consumer naiveté.
A WIRED journalist wrote that "23andMe has been sharing insights gleaned from consented customer data with GSK and at least six other pharmaceutical and biotechnology firms for the past three and a half years." Is this a consumer privacy risk?
I don't see that 23andMe did anything to which consumers didn't consent, albeit through arguably unreadable terms and conditions. The part that worries me more is the 300 phenotype data points that the company has collected on its consumers through longitudinal surveys designed, as Anne Wojcicki, CEO and Co-founder of 23andMe, put it, "to circumvent medical records and just self-report."
Everyone is focused on the DNA, but it's the combination of genetic samples, genealogical information and health records that is the most potent dataset, and 23andMe has figured out a way to extract all three from consumers.
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.