“Getting a medical exam feels like we’re still in the nineties,” says Taavet Hinrikus, co-founder of health startup Certific. He thinks medical testing is broken. “You ask for one over the phone, you have to go to a medical practice, register, wait around for the doctor, then wait days for the results to arrive.” This, he concluded, was a massive waste of patient’s and doctor’s time.
“If you think about the way we’re used to consuming modern services, it just doesn’t quite add up,” he said, citing a few examples. If you want to make a long-distance phone call, you don’t need to talk to an operator to connect you. Instead, you use Skype. If you want to send money overseas, you no longer need to go to a bank branch and pay extortionate exchange rates. Rather, you use Wise. These examples, of course, are not random. Hinrikus was Skype’s first employee and, later, became co-founder of TransferWise (recently renamed Wise). What sets these products apart, according to him, is that they aren’t simply better. To succeed they had to become vastly better across a number of categories, including pricing, speed and transparency.
“These are examples of products that have become ten times better over the years,” he said. He recalled his early days at Skype, in 2003, trying to make the first voice calls. “I was in a badly lit corridor on the outskirts of soviet Estonia,” he recalled. “Computers didn't come equipped with microphones. It was hard to find where to plug in a headset. New solutions usually start out like a toy. Yet when the toys start improving at considerable speed then what was once laughed upon becomes a power tool.”
The same revolution, he said, is now possible in the medical world. “In discussions with collaborators, we kept talking about the need for a Skype moment for medical testing,” he said. “We needed to make it ten times better.” The answer came in February 2021, when Hinrikus, alongside Liis Narusk and healthcare entrepreneur and longtime WIRED Health collaborator Jack Kreindler, founded Certific, a startup that aims to provide cheaper and faster remote Covid testing. The app can be used to easily book a Covid test, verifying users’ identities and providing video instructions showing how to correctly swab yourself. The results, based on PCR tests at the moment, are then sent to a lab, verified by Certific’s medical staff. A digital certification and a QR code containing the test result is issued to the user on the app by the following day. Currently, tests are only available in the UK and cost £64 per person.
For now, Certific is focused on issuing certifications for large-scale in-person events and international travel. “While we have learned to love virtual conferences, they have not replaced a real-life element of meeting with people,” Henrikus said. “The solution now still looks a bit like a toy, but very soon will be an indispensable power tool to be used globally.”
Henrikus was speaking at WIRED Health 2021, on March 31. He appeared alongside leading doctors, technologists and medical professionals who explained where healthcare is going next. Here how things are changing.
AI will find new drugs
In January 2020, Joanna Shields, CEO of healthtech company Benevolent AI, asked her team to start looking into the Covid-19 epidemic that was emerging in Wuhan, China. “We rapidly pivoted our research towards understanding the body’s response to the virus,” Shields said at WIRED Health 2021. “The specialist team mobilised to identify existing drugs already proven safe that could treat the virus until vaccines were developed and available.”
The team applied Benevolent’s natural language processing and relationship extraction algorithms to the datasets of curated biomedical information about the virus that were being rapidly shared by researchers around the world. “The scientists focused first on identifying the mechanism by which the virus enters the cells,” Shields said. “Then they queried the platform for drugs that had properties that could inhibit viral entry, block viral replication and had an anti-inflammatory response to help ameliorate the cytokine storm which was proving to be so deadly in Covid patients.”
The results were almost immediate: in a few hours, they were able to identify baricitinib, a drug for the treatment of rheumatoid arthritis. “It was logical to examine the potential of anti-inflammatory drugs for Covid-19,” Shields recalled. “However, we uncovered previously unknown antiviral properties of this compound.” These properties, which stopped the virus from infecting cells and dampened the body’s extreme immune response, came as a surprise even to the drug manufacturer, the pharma company Eli Lilly. “It’s safe to say that no scientist would have seen this signal in the data without the support of AI and machine learning,” Shields said.
Benevolent’s findings were published in the medical journal The Lancet on February 4, 2020. In a subsequent study, researchers from Imperial College and the Karolinska Institute independently verified Benevolent’s report in the laboratory. In April, the National Institute of Allergy and Infectious Diseases (NIAID) kick-started a large-scale randomised clinical trial. The results were published seven months later in Science, showing that the drug contributed to a 71 per cent reduction in mortality in elderly patients with Covid-19. Shortly after, baricitinib received an FDA emergency use authorisation. “It’s now being administered in patients in the US alongside remdesevir,” Shields said, adding that this was the first ever case of a drug discovered by AI to be validated in a large-scale clinical trial and receiving FDA approval. “We went from computer to lab bench to bedside in a record time.”
For Shields, this discovery reflects the importance of quality biomedical data, especially during a pandemic, when more than 200,000 scientific papers related to the virus have been published. “It’s simply impossible for scientists to synthesise this vast universe of information and make sense of it all,” she said. “Traditional ways of harvesting data are time-consuming and error-prone and expensive.”
Shields, who is also the co-chair of the Global Partnership on AI, urged governments and scientists to build open research and data sharing partnerships that could help accelerate the response to the pandemic now, and prevent new ones in the future. “Data is the lifeblood of AI powered research,” she said. “Ultimately, algorithms are only as good as the data we use to train them. Machine learning models can interrogate vast quantities of biomedical information and yet the quality of that data directly impacts the value of hypotheses generated.”
Health monitoring is improving
Celine Gounder, an infectious disease expert at New York University and a key member of president Biden’s Covid Task Force, started her WIRED Health 2021 talk with the good news: within the first 100 days of the Biden administration, they were able to vaccinate 200 million people. “That’s double the original target,” Gounder said. “A couple of months ago, I was very sceptical we could do even 100 million shots in arms, but the pharmaceutical companies really have come through with the supply that we need to distribute and massively ramp up our distribution capacity.” Furthermore, she said, over 70 for cent of Americans over the age of 65 and about a third of US adults have received one dose of the vaccine, and more than 50 per cent have been fully inoculated. “We are reaching three million doses in arms a day on some days now,” she added. “By May 1, all American adults will be able to be vaccinated.”
According to Gounder, the Biden vaccination plan achieved this with measures by expanding vaccination sites across the country and providing free transport for disabled and senior people to vaccination sites. Soon, she said, 90 per cent of the US population will also be within five miles of a vaccination site. “We’re going to more than double retail pharmacies that are distributing vaccines, going from about 17,000 sites to 40,000 sites across the country, and we’re also increasing the number of FEMA mass vaccination sites.” She also made the point that over 60 per cent of the shots given at the mass vaccination sites were going to the communities who had been hit hard during the pandemic. “They've been really an important tool in making sure that we have an equitable distribution of the vaccines,” she said.
Of course, this pandemic is still far from over. In the US, Gounder was seeing the early signs of a new Covid-19 surge with over 70,000 new cases daily, while deaths remain at about 1,000 a day. “There is no question that people are relaxing on some of the mitigation measures: governors are lifting mask mandates, we're reopening indoor businesses including restaurants and bars and gyms, and we're not adhering to as as much social distancing,” she said.
Gounder is also concerned with the rapid spread of new variants, in particular the B117 variant, which originated in the UK. “This variant is more infectious and more virulent,” Gounder said. “We're also seeing more severe cases of Covid among people in their thirties, forties and fifties, who have not been vaccinated yet.” Stopping the spread of these new variants will require, for instance, expanding the country’s genomic surveillance, similarly to what has been achieved in the UK.
“The vaccines are truly revolutionary,” Gounder said. “They're highly effective, they're very safe, but they're not perfect. They are like a good raincoat and an umbrella – great for keeping you safe and dry in a regular thunderstorm, but right now we're dealing with a Covid hurricane, so those measures aren’t enough. If you're vaccinated, you still need to wear a mask when you're out in public and should be avoiding crowds.”
mRNA will create new vaccines
When Ugur Sahin, CEO of German company BioNTech, first spoke at WIRED Health in 2020, he said he expected his Covid vaccine to ideally have an efficacy of about 60 per cent. “I knew that we had an almost perfect vaccine, because we understand how to activate the components of the immune system,” Sahin said. “What was not known was the enemy, how sensitive was the virus.” A few weeks later, BioNTech made its first public announcement confirming the final results of the phase three clinical trial: the BioNTech vaccine had an efficacy of 95 per cent. “It turned out that we were able to hit the virus really in a precise fashion, with very high efficacy,” he said.
To Sahin and his close collaborators, this success was the result of a journey that started 25 years ago, when he first began exploring the technology of messenger RNA. “Messenger RNA is a molecule which is used by human body cells to provide information to build proteins in the cells,” he explained. “The idea of a messenger RNA therapeutics is to use this molecule to deliver information to human cells. If you deliver information to teach the immune system about the pathogen, in this case the virus, you have a vaccine.”
The first application for the messenger RNA technology was in cancer immunotherapies. By the end of 2019, BioNTech had multiple cancer programs, including one aiming to develop personalised cancer vaccines: “The idea behind that is to get a piece of genetic information from the tumor and make a vaccine in the shortest possible time for the individual,” Sahin said. “We had the ability to engineer mRNA vaccines according to genetic sequences. It usually takes years to do something like that and we had established technologies allowing us to make a drug within a few weeks.”
In January 2020, however, everything changed. Alerted by the quickly spreading Covid-19 epidemic situation in Wuhan, BioNTech decided to start developing a vaccine for the new virus. “We started by creating 20 vaccine candidates,” Sahin recalls “It was not clear which was the best vaccine candidate, as we did not know much about the virus.” With a clinical trial already planned to start in April that year, they contacted US pharma company Pfizer to help speed up the process. “We called it Project Lightspeed,” Sahin says. “We wanted to make clear that we didn't have time to waste and that we will go with in the fastest possible way without considering traditional ways of vaccine development – where you do things sequentially, you don't work on the weekends, you don't work evenings. Instead, we built a 24/7 programme and did many things in parallel.”
After delivering a successful vaccine candidate, manufacturing it at scale represented a very different challenge for BioNTech and Pfizer. “At the end of 2019, our technology allowed us to make 10,000 vaccine doses,” Sahin said. “We had to scale up that manufacturing factor by a range of 300,000.” Various vaccine components are produced by different manufacturers worldwide, so BioNTech had to create a collaborative network of multiple companies worldwide. “For instance, when we asked companies to make us the lipid nanoparticles at those scales, they said they couldn’t do it, that it would take 18 months,” he said. “We needed to be much faster. We had to put all these other companies in the Lightspeed mode.”
Looking forward, Sahin is aware that his accomplishment represents a milestone – the approval of the first mRNA drug in history – that can change everything. “This opens up a completely new industry,” he said. “We want to develop products for infectious disease and cancer, but we also want to build a new kind of biopharmaceutical company to deliver medicines which reduce suffering in many kinds of diseases. Covid-19 is just the beginning.”
Genetic editing can eliminate viruses
We’re in an exponential revolution in genomics, George Church told the audience at WIRED Health 2021. “The human genome originally cost three billion dollars and wasn’t that clinically useful. In just a decade, we’ve improved 20-million-fold in terms of cost and a 100,000-fold in terms of quality.” This revolution, according to Church, is mostly thanks to the technique of molecular multiplexing. “It can be used for cells, for reading and writing of all sorts of biology,” he said. “One example of that on everybody’s mind is gene editing, which is mostly what CRISPR does. There are many different enzymes involved, but the key is the delivery of these enzymes to the right cells in the right location in the genome.”
These new genetic editing techniques allow, for instance, to eliminate most viruses. “One strategy for getting rid of all viruses is by codon recoding,” he said. “Taking one or two codon and completely remapping them to a synonymous one.” Church presented research showing the benefits to such recoded organisms. “This is a way whereby making a large number of changes in the genome makes you resistant to nearly all viruses,” he said. “We’re now on our way to applying this to multiple organisms and all viruses. We think it’s generalisable to any organism.”
Another example was the application of editing techniques in gene therapy, particularly by manipulating the receptors in viruses. “That’s aimed at solving the transplantation crisis, where millions of people could benefit from some sort of cell or organ therapy,” he said. “To that end, we’ve created what we call a pig version 3.0. This involved 24 changes in the genome, most of which involved getting rid of endogenous viruses. Many of us, including humans and pigs, have endogenous viruses which are potentially quite serious when you suddenly receive a new organ, especially in immunosuppressed patients.” The new pigs were made to be immune and biochemically compatible with the donors. Researchers are now looking to start the first non-human primate clinical trials.
Church also mentioned the promising work of harnessing viruses – so-called adeno-associated viruses (AAV) – for gene therapies. “We have various gene therapies, like using CAR T-cells to treat blood cancers like B-cell leukaemia.” There are problems, however, when delivering these treatments using AAV, related to the body’s immune response against these cells and how to deliver them to specific tissues in the body. “We get around this by designing millions of mutations, implemented via DNA synthesis, and by using machine learning. This could be done by systematically changing each amino acid at the time, but now we can change the genome with up to 29 mutations at the time. It used to be hard to change more than four mutations at a time because that would cause the virus or the organism to die, but now with machine learning we can get up to these high numbers.”
We’ll learn from isolation
Medical doctor Beth Healey has worked in some of the most extreme and remote environments, from Greenland to Antarctica, studying the physiological and psychological effects of isolation on teams of scientists. “I was at the Concordia platform in Antarctica,” Healey said. There, crews have to withstand temperatures reaching minus 80 degrees Celsius and more than 105 days without seeing any sunlight. “We’re also completely inaccessible for nine months of the year, even in case of emergency. This is really interesting for space agencies because as we're looking at going further and deeper into space, astronauts are going to be increasingly isolated.”
The Concordia expedition was part of her research on the challenges of future space missions, studying human behaviour in these overwintering crews. “But there’s a huge emphasis on what it’s like to come back home afterwards too,” she said. “I was really excited about going home, but I think a lot of us felt pretty lost. This is something that a lot of people can relate to with the current pandemic and coming out of lockdown.”
Healey mentioned how, on being back to London, she had to reintegrate into life back home and readjust to many normal aspects of life: she felt socially awkward in large groups of people, felt nervous going on buses, had to relearn how to drive. “Life in Antarctica is very simple, you don’t have the distractions that you have in a normal life,” she said. “People struggled when they sort of tried to go back to their normal lives, just because of all the chaos, and making decisions like having to choose between, like, 60 different brands of washing powder.”
This transformation was also reflected in a research study. Healey took part in a Nasa science project which involved taking brain scans just before and immediately after her mission, and then six months later. “We do see functional changes in our brains on the MRI scans after that period of isolation, but that did resolve after we’d spent some time back,” she said. “It's not that you forget how to do things, you just become a little bit more inefficient at doing them. I was just a little bit slow and clunky. And I tragically forgot my PIN number, which is just what they had said was going to happen, and I just didn’t believe it would happen to me.”
Nevertheless, there can be positives to such extreme experiences of isolation. One example is a renewed sense of community. “A sort of shared goal, which we’re all working towards,” Healey said. She felt that particularly after returning to London and working on the Covid ICU wards. “Treating patients with Coronavirus has really brought us together as a healthcare system. I really hope that that sense of camaraderie continues.”
Another positive aspect that Healey highlighted is what astronauts call the overview effect. “What they're talking about is looking back and offering that sort of fresh perspective on how they see the world,” she said. “Well, during the pandemic, of course we haven't been to space or Antarctica, but do you think that it has offered us the opportunity to really sort of step back from our day to day lives and think about what it is that we want to do in the future and what we want in that future to be?”
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This article was originally published by WIRED UK
