Medical Breakthroughs Set to be Fast-Tracked by Innovative New Health Agency
Pippy Rogers, second from left, with her four siblings, who worry that they are at risk for Alzheimer's and are calling for an acceleration of research.
In 2007, Matthew Might's son, Bertrand, was born with a life-threatening disease that was so rare, doctors couldn't diagnose it. Might, a computer scientist and biologist, eventually realized, "Oh my gosh, he's the only patient in the world with this disease right now." To find effective treatments, new methodologies would need to be developed. But there was no process or playbook for doing that.
Might took it upon himself, along with a team of specialists, to try to find a cure. "What Bertrand really taught me was the visceral sense of urgency when there's suffering, and how to act on that," he said.
He calls it "the agency of urgency"—and patients with more common diseases, such as cancer and Alzheimer's, often feel that same need to take matters into their own hands, as they find their hopes for new treatments running up against bureaucratic systems designed to advance in small, steady steps, not leaps and bounds. "We all hope for a cure," said Florence "Pippy" Rogers, a 65-year-old volunteer with Georgia's chapter of the Alzheimer's Association. She lost her mother to the disease and, these days, worries about herself and her four siblings. "We need to keep accelerating research."
We have a fresh example of what can be achieved by fast-tracking discoveries in healthcare: Covid-19 vaccines.
President Biden has pushed for cancer moonshots since the disease took the life of his son, Beau, in 2015. His administration has now requested $6.5 billion to start a new agency in 2022, called the Advanced Research Projects Agency for Health, or ARPA-H, within the National Institutes of Health. It's based on DARPA, the Department of Defense agency known for hatching world-changing technologies such as drones, GPS and ARPANET, which became the internet.
We have a fresh example of what can be achieved by fast-tracking discoveries in healthcare: Covid-19 vaccines. "Operation Warp Speed was using ARPA-like principles," said Might. "It showed that in a moment of crisis, institutions like NIH can think in an ARPA-like way. So now the question is, why don't we do that all the time?"
But applying the DARPA model to health involves several challenging decisions. I asked experts what could be the hardest question facing advocates of ARPA-H: which health problems it should seek to address. "All the wonderful choices lead to the problem of which ones to choose and prioritize," said Sudip Parikh, CEO of the American Association for the Advancement of Science and executive publisher of the Science family of journals. "There is no objectively right answer."
The Agency of Urgency
ARPA-H will borrow at least three critical ingredients from DARPA: goal-oriented project managers, many from industry; aggressive public-private partnerships; and collaboration among fields that don't always interact. The DARPA concept has been applied to other purposes, including energy and homeland security, with promising results. "We're learning that 'ARPA-ism' is a franchisable model," said Might, a former principal investigator on DARPA projects.
The federal government already pours billions of dollars into advancing research on life-threatening diseases, with much of it channeled through the National Institutes of Health. But the purpose of ARPA-H "isn't just the usual suspects that NIH would fund," said David Walt, a Harvard biochemist, an innovator in gene sequencing and former chair of DARPA's Defense Science Research Council. Whereas some NIH-funded studies aim to gradually improve our understanding of diseases, ARPA-H projects will give full focus to real-world applications; they'll use essential findings from NIH research as starting points, drawing from them to rapidly engineer new technologies that could save lives.
And, ultimately, billions in healthcare costs, if ARPA-H lives up to its predecessor's track record; DARPA's breakthroughs have been economic game-changers, while its fail-fast approach—quickly pulling the plug on projects that aren't panning out—helps to avoid sunken costs. ARPA-H could fuel activities similar to the human genome project, which used existing research to map the base pairs that make up DNA, opening new doors for the biotech industry, sparking economic growth and creating hundreds of thousands of new jobs.
Despite a nearly $4 trillion health economy, "we aren't innovating when it comes to technological capabilities for health," said Liz Feld, president of the Suzanne Wright Foundation for pancreatic cancer.
Individual Diseases Ripe for Innovation
Although the need for innovation is clear, which diseases ARPA-H should tackle is less apparent. One important consideration when choosing health priorities could be "how many people suffer from a disease," said Nancy Kass, a professor of bioethics and public health at Johns Hopkins.
That perspective could justify cancer as a top objective. Cancer and heart disease have long been the two major killers in the U.S. Leonidas Platanias, professor of oncology at Northwestern and director of its cancer center, noted that we've already made significant progress on heart disease. "Anti-cholesterol drugs really have a wide impact," he said. "I don't want to compare one disease to another, but I think cancer may be the most challenging. We need even bigger breakthroughs." He wondered whether ARPA-H should be linked to the part of NIH dedicated to cancer, the National Cancer Institute, "to take maximum advantage of what happens" there.
Previous cancer moonshots have laid a foundation for success. And this sort of disease-by-disease approach makes sense in a way. "We know that concentrating on some diseases has led to treatments," said Parikh. "Think of spinal muscular atrophy or cystic fibrosis. Now, imagine if immune therapies were discovered ten years earlier."
But many advocates think ARPA-H should choose projects that don't revolve around any one disease. "It absolutely has to be disease agnostic," said Feld, president of the pancreatic cancer foundation. "We cannot reach ARPA-H's potential if it's subject to the advocacy of individual patient groups who think their disease is worse than the guy's disease next to them. That's not the way the DARPA model works." Platanias agreed that ARPA-H should "pick the highest concepts and developments that have the best chance" of success.
Finding Connections Between Diseases
Kass, the Hopkins bioethicist, believes that ARPA-H should walk a balance, with some projects focusing on specific diseases and others aspiring to solutions with broader applications, spanning multiple diseases. Being impartial, some have noted, might involve looking at the total "life years" saved by a health innovation; the more diseases addressed by a given breakthrough, the more years of healthy living it may confer. The social and economic value should increase as well.
For multiple payoffs, ARPA-H could concentrate on rare diseases, which can yield important insights for many other diseases, said Might. Every case of cancer and Alzheimer's is, in a way, its own rare disease. Cancer is a genetic disease, like his son Bertrand's rare disorder, and mutations vary widely across cancer patients. "It's safe to say that no two people have ever actually had the same cancer," said Might. In theory, solutions for rare diseases could help us understand how to individualize treatments for more common diseases.
Many experts I talked with support another priority for ARPA-H with implications for multiple diseases: therapies that slow down the aging process. "Aging is the greatest risk factor for every major disease that NIH is studying," said Matt Kaeberlein, a bio-gerontologist at the University of Washington. Yet, "half of one percent of the NIH budget goes to researching the biology of aging. An ARPA-H sized budget would push the field forward at a pace that's hard to imagine."
Might agreed. "It could take ARPA-H to get past the weird stigmas around aging-related research. It could have a tremendous impact on the field."
For example, ARPA-H could try to use mRNA technology to express proteins that affect biological aging, said Kaeberlein. It's an engineering project well-suited to the DARPA model. So is harnessing machine learning to identify biomarkers that assess how fast people are aging. Biological aging clocks, if validated, could quickly reveal whether proposed therapies for aging are working or not. "I think there's huge value in that," said Kaeberlein.
By delivering breakthroughs in computation, ARPA-H could improve diagnostics for many different diseases. That could include improving biowearables for continuously monitoring blood pressure—a hypothetical mentioned in the White House's concept paper on ARPA-H—and advanced imaging technologies. "The high cost of medical imaging is a leading reason why our healthcare costs are the highest in the world," said Feld. "There's no detection test for ALS. No brain detection for Alzheimer's. Innovations in detection technology would save on cost and human suffering."
Some biotech companies may be skeptical about the financial rewards of accelerating such technologies. But ARPA-H could fund public-private partnerships to "de-risk" biotech's involvement—an incentive that harkens back to the advance purchase contracts that companies got during Covid. (Some groups have suggested that ARPA-H could provide advance purchase agreements.)
Parikh is less bullish on creating diagnostics through ARPA-H. Like DARPA, Biden's health agency will enjoy some independence from federal oversight; it may even be located hundreds of miles from DC. That freedom affords some breathing room for innovation, but it could also make it tougher to ensure that algorithms fully consider diverse populations. "That part I really would like the government more involved in," Parikh said.
Might thinks ARPA-H should also explore innovations in clinical trials, which many patients and medical communities view as grindingly slow and requiring too many participants. "We can approve drugs for very tiny patient populations, even at the level of the individual," he said, while emphasizing the need for safety. But Platanias thinks the FDA has become much more flexible in recent years. In the cancer field, at least, "You now see faster approvals for more drugs. Having [more] shortcuts on clinical trial approvals is not necessarily a good idea."
With so many options on the table, ARPA-H needs to show the public a clear framework for measuring the value of potential projects. Kass warned that well-resourced advocates could skew the agency's priorities. They've affected health outcomes before, she noted; fundraising may partly explain larger increases in life expectancy for cystic fibrosis than sickle cell anemia. Engaging diverse communities is a must for ARPA-H. So are partnerships to get the agency's outputs to people who need them. "Research is half the equation," said Kass. "If we don't ensure implementation and access, who cares." The White House concept paper on ARPA-H made a similar point.
As Congress works on authorizing ARPA-H this year, Might is doing what he can to ensure better access to innovation on a patient-by-patient basis. Last year, his son, Bertrand, passed away suddenly from his disorder. He was 12. But Might's sense of urgency has persisted, as he directs the Precision Medicine Institute at the University of Alabama-Birmingham. That urgency "can be carried into an agency like ARPA-H," he said. "It guides what I do as I apply for funding, because I'm trying to build the infrastructure that other parents need. So they don't have to build it from scratch like I did."
Urinary tract infections account for more than 8 million trips to the doctor each year.
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”
MILESTONE: Doctors have transplanted a pig organ into a human for the first time in history
A surgeon at Massachusetts General Hospital prepares a pig organ for transplant.
Surgeons at Massachusetts General Hospital made history last week when they successfully transplanted a pig kidney into a human patient for the first time ever.
The recipient was a 62-year-old man named Richard Slayman who had been living with end-stage kidney disease caused by diabetes. While Slayman had received a kidney transplant in 2018 from a human donor, his diabetes ultimately caused the kidney to fail less than five years after the transplant. Slayman had undergone dialysis ever since—a procedure that uses an artificial kidney to remove waste products from a person’s blood when the kidneys are unable to—but the dialysis frequently caused blood clots and other complications that landed him in the hospital multiple times.
As a last resort, Slayman’s kidney specialist suggested a transplant using a pig kidney provided by eGenesis, a pharmaceutical company based in Cambridge, Mass. The highly experimental surgery was made possible with the Food and Drug Administration’s “compassionate use” initiative, which allows patients with life-threatening medical conditions access to experimental treatments.
The new frontier of organ donation
Like Slayman, more than 100,000 people are currently on the national organ transplant waiting list, and roughly 17 people die every day waiting for an available organ. To make up for the shortage of human organs, scientists have been experimenting for the past several decades with using organs from animals such as pigs—a new field of medicine known as xenotransplantation. But putting an animal organ into a human body is much more complicated than it might appear, experts say.
“The human immune system reacts incredibly violently to a pig organ, much more so than a human organ,” said Dr. Joren Madsen, director of the Mass General Transplant Center. Even with immunosuppressant drugs that suppress the body’s ability to reject the transplant organ, Madsen said, a human body would reject an animal organ “within minutes.”
So scientists have had to use gene-editing technology to change the animal organs so that they would work inside a human body. The pig kidney in Slayman’s surgery, for instance, had been genetically altered using CRISPR-Cas9 technology to remove harmful pig genes and add human ones. The kidney was also edited to remove pig viruses that could potentially infect a human after transplant.
With CRISPR technology, scientists have been able to prove that interspecies organ transplants are not only possible, but may be able to successfully work long term, too. In the past several years, scientists were able to transplant a pig kidney into a monkey and have the monkey survive for more than two years. More recently, doctors have transplanted pig hearts into human beings—though each recipient of a pig heart only managed to live a couple of months after the transplant. In one of the patients, researchers noted evidence of a pig virus in the man’s heart that had not been identified before the surgery and could be a possible explanation for his heart failure.
So far, so good
Slayman and his medical team ultimately decided to pursue the surgery—and the risk paid off. When the pig organ started producing urine at the end of the four-hour surgery, the entire operating room erupted in applause.
Slayman is currently receiving an infusion of immunosuppressant drugs to prevent the kidney from being rejected, while his doctors monitor the kidney’s function with frequent ultrasounds. Slayman is reported to be “recovering well” at Massachusetts General Hospital and is expected to be discharged within the next several days.