The World’s Most Famous Billionaires Are Joining Forces to Fight Alzheimer’s
Phil Gutis never had a stellar memory, but when he reached his early 50s, it became a problem he could no longer ignore. He had trouble calculating how much to tip after a meal, finding things he had just put on his desk, and understanding simple driving directions.
From 1998-2017, industry sources reported 146 failed attempts at developing Alzheimer's drugs.
So three years ago, at age 54, he answered an ad for a drug trial seeking people experiencing memory issues. He scored so low in the memory testing he was told something was wrong. M.R.I.s and PET scans confirmed that he had early-onset Alzheimer's disease.
Gutis, who is a former New York Times reporter and American Civil Liberties Union spokesman, felt fortunate to get into an advanced clinical trial of a new treatment for Alzheimer's disease. The drug, called aducanumab, had shown promising results in earlier studies.
Four years of data had found that the drug effectively reduced the burden of protein fragments called beta-amyloids, which destroy connections between nerve cells. Amyloid plaques are found in the brains of patients with Alzheimer's disease and are associated with impairments in thinking and memory.
Gutis eagerly participated in the clinical trial and received 35 monthly infusions. "For the first 20 infusions, I did not know whether I was receiving the drug or the placebo," he says. "During the last 15 months, I received aducanumab. But it really didn't matter if I was receiving the drug or the placebo because on March 21, the trial was stopped because [the drug company] Biogen found that the treatments were ineffective."
The news was devastating to the trial participants, but also to the Alzheimer's research community. Earlier this year, another pharmaceutical company, Roche, announced it was discontinuing two of its Alzheimer's clinical trials. From 1998-2017, industry sources reported 146 failed attempts at developing Alzheimer's drugs. There are five prescription drugs approved to treat its symptoms, but a cure remains elusive. The latest failures have left researchers scratching their heads about how to approach attacking the disease.
The failure of aducanumab was also another setback for the estimated 5.8 million people who have Alzheimer's in the United States. Of these, around 5.6 million are older than 65 and 200,000 suffer from the younger-onset form, including Gutis.
Gutis is understandably distraught about the cancellation of the trial. "I really had hopes it would work. So did all the patients."
While drug companies have failed so far, another group is stepping up to expedite the development of a cure: venture philanthropists.
For now, he is exercising every day to keep his blood flowing, which is supposed to delay the progression of the disease, and trying to eat a low-fat diet. "But I know that none of it will make a difference. Alzheimer's is a progressive disease. There are no treatments to delay it, let alone cure it."
But while drug companies have failed so far, another group is stepping up to expedite the development of a cure: venture philanthropists. These are successful titans of industry and dedicated foundations who are donating large sums of money to fill a much-needed void – funding research to look for new biomarkers.
Biomarkers are neurochemical indicators that can be used to detect the presence of a disease and objectively measure its progression. There are currently no validated biomarkers for Alzheimer's, but researchers are actively studying promising candidates. The hope is that they will find a reliable way to identify the disease even before the symptoms of mental decline show up, so that treatments can be directed at a very early stage.
Howard Fillit, Founding Executive Director and Chief Science Officer of the Alzheimer's Drug Discovery Foundation, says, "We need novel biomarkers to diagnose Alzheimer's disease and related dementias. But pharmaceutical companies don't put money into biomarkers research."
One of the venture philanthropists who has recently stepped up to the task is Bill Gates. In January 2018, he announced his father had Alzheimer's disease in an interview on the Today Show with Maria Shriver, whose father Sargent Shriver, died of Alzheimer's disease in 2011. Gates told Ms. Shriver that he had invested $100 million into Alzheimer's research, with $50 million of his donation going to Dementia Discovery Fund, which looks for new cures and treatments.
That August, Gates joined other investors in a new fund called Diagnostics Accelerator. The project aims to supports researchers looking to speed up new ideas for earlier and better diagnosis of the disease.
Gates and other donors committed more than $35 million to help launch it, and this April, Jeff and Mackenzie Bezos joined the coalition, bringing the current program funding to nearly $50 million.
"It makes sense that a challenge this significant would draw the attention of some of the world's leading thinkers."
None of these funders stand to make a profit on their donation, unlike traditional research investments by drug companies. The standard alternatives to such funding have upsides -- and downsides.
As Bill Gates wrote on his blog, "Investments from governments or charitable organizations are fantastic at generating new ideas and cutting-edge research -- but they're not always great at creating usable products, since no one stands to make a profit at the end of the day.
"Venture capital, on the other end of the spectrum, is more likely to develop a test that will reach patients, but its financial model favors projects that will earn big returns for investors. Venture philanthropy splits the difference. It incentivizes a bold, risk-taking approach to research with an end goal of a real product for real patients. If any of the projects backed by Diagnostics Accelerator succeed, our share of the financial windfall goes right back into the fund."
Gutis said he is thankful for any attention given to finding a cure for Alzheimer's.
"Most doctors and scientists will tell you that we're still in the dark ages when it comes to fully understanding how the brain works, let alone figuring out the cause or treatment for Alzheimer's.
"It makes sense that a challenge this significant would draw the attention of some of the world's leading thinkers. I only hope they can be more successful with their entrepreneurial approach to finding a cure than the drug companies have been with their more traditional paths."
Bivalent Boosters for Young Children Are Elusive. The Search Is On for Ways to Improve Access.
It’s Theo’s* first time in the snow. Wide-eyed, he totters outside holding his father’s hand. Sarah Holmes feels great joy in watching her 18-month-old son experience the world, “His genuine wonder and excitement gives me so much hope.”
In the summer of 2021, two months after Theo was born, Holmes, a behavioral health provider in Nebraska lost her grandparents to COVID-19. Both were vaccinated and thought they could unmask without any risk. “My grandfather was a veteran, and really trusted the government and faith leaders saying that COVID-19 wasn’t a threat anymore,” she says.” The state of emergency in Louisiana had ended and that was the message from the people they respected. “That is what killed them.”
The current official public health messaging is that regardless of what variant is circulating, the best way to be protected is to get vaccinated. These warnings no longer mention masking, or any of the other Swiss-cheese layers of mitigation that were prevalent in the early days of this ongoing pandemic.
The problem with the prevailing, vaccine centered strategy is that if you are a parent with children under five, barriers to access are real. In many cases, meaningful tools and changes that would address these obstacles are lacking, such as offering vaccines at more locations, mandating masks at these sites, and providing paid leave time to get the shots.
Children are at risk
Data presented at the most recent FDA advisory panel on COVID-19 vaccines showed that in the last year infants under six months had the third highest rate of hospitalization. “From the beginning, the message has been that kids don’t get COVID, and then the message was, well kids get COVID, but it’s not serious,” says Elias Kass, a pediatrician in Seattle. “Then they waited so long on the initial vaccines that by the time kids could get vaccinated, the majority of them had been infected.”
A closer look at the data from the CDC also reveals that from January 2022 to January 2023 children aged 6 to 23 months were more likely to be hospitalized than all other vaccine eligible pediatric age groups.
“We sort of forced an entire generation of kids to be infected with a novel virus and just don't give a shit, like nobody cares about kids,” Kass says. In some cases, COVID has wreaked havoc with the immune systems of very young children at his practice, making them vulnerable to other illnesses, he said. “And now we have kids that have had COVID two or three times, and we don’t know what is going to happen to them.”
Jumping through hurdles
Children under five were the last group to have an emergency use authorization (EUA) granted for the COVID-19 vaccine, a year and a half after adult vaccine approval. In June 2022, 30,000 sites were initially available for children across the country. Six months later, when boosters became available, there were only 5,000.
Currently, only 3.8% of children under two have completed a primary series, according to the CDC. An even more abysmal 0.2% under two have gotten a booster.
Ariadne Labs, a health center affiliated with Harvard, is trying to understand why these gaps exist. In conjunction with Boston Children’s Hospital, they have created a vaccine equity planner that maps the locations of vaccine deserts based on factors such as social vulnerability indexes and transportation access.
“People are having to travel farther because the sites are just few and far between,” says Benjy Renton, a research assistant at Ariadne.
Michelle Baltes-Breitwisch, a pharmacist, and her two-year-old daughter, Charlee, live in Iowa. When the boosters first came out she expected her toddler could get it close to home, but her husband had to drive Charlee four hours roundtrip.
This experience hasn’t been uncommon, especially in rural parts of the U.S. If parents wanted vaccines for their young children shortly after approval, they faced the prospect of loading babies and toddlers, famous for their calm demeanor, into cars for lengthy rides. The situation continues today. Mrs. Smith*, a grant writer and non-profit advisor who lives in Idaho, is still unable to get her child the bivalent booster because a two-hour one-way drive in winter weather isn’t possible.
It can be more difficult for low wage earners to take time off, which poses challenges especially in a number of rural counties across the country, where weekend hours for getting the shots may be limited.
Protect Their Future (PTF), a grassroots organization focusing on advocacy for the health care of children, hears from parents several times a week who are having trouble finding vaccines. The vaccine rollout “has been a total mess,” says Tamara Lea Spira, co-founder of PTF “It’s been very hard for people to access vaccines for children, particularly those under three.”
Seventeen states have passed laws that give pharmacists authority to vaccinate as young as six months. Under federal law, the minimum age in other states is three. Even in the states that allow vaccination of toddlers, each pharmacy chain varies. Some require prescriptions.
It takes time to make phone calls to confirm availability and book appointments online. “So it means that the parents who are getting their children vaccinated are those who are even more motivated and with the time and the resources to understand whether and how their kids can get vaccinated,” says Tiffany Green, an associate professor in population health sciences at the University of Wisconsin at Madison.
Green adds, “And then we have the contraction of vaccine availability in terms of sites…who is most likely to be affected? It's the usual suspects, children of color, disabled children, low-income children.”
It can be more difficult for low wage earners to take time off, which poses challenges especially in a number of rural counties across the country, where weekend hours for getting the shots may be limited. In Bibb County, Ala., vaccinations take place only on Wednesdays from 1:45 to 3:00 pm.
“People who are focused on putting food on the table or stressed about having enough money to pay rent aren't going to prioritize getting vaccinated that day,” says Julia Raifman, assistant professor of health law, policy and management at Boston University. She created the COVID-19 U.S. State Policy Database, which tracks state health and economic policies related to the pandemic.
Most states in the U.S. lack paid sick leave policies, and the average paid sick days with private employers is about one week. Green says, “I think COVID should have been a wake-up call that this is necessary.”
Maskless waiting rooms
For her son, Holmes spent hours making phone calls but could uncover no clear answers. No one could estimate an arrival date for the booster. “It disappoints me greatly that the process for locating COVID-19 vaccinations for young children requires so much legwork in terms of time and resources,” she says.
In January, she found a pharmacy 30 minutes away that could vaccinate Theo. With her son being too young to mask, she waited in the car with him as long as possible to avoid a busy, maskless waiting room.
Kids under two, such as Theo, are advised not to wear masks, which make it too hard for them to breathe. With masking policies a rarity these days, waiting rooms for vaccines present another barrier to access. Even in healthcare settings, current CDC guidance only requires masking during high transmission or when treating COVID positive patients directly.
“This is a group that is really left behind,” says Raifman. “They cannot wear masks themselves. They really depend on others around them wearing masks. There's not even one train car they can go on if their parents need to take public transportation… and not risk COVID transmission.”
Yet another challenge is presented for those who don’t speak English or Spanish. According to Translators without Borders, 65 million people in America speak a language other than English. Most state departments of health have a COVID-19 web page that redirects to the federal vaccines.gov in English, with an option to translate to Spanish only.
The main avenue for accessing information on vaccines relies on an internet connection, but 22 percent of rural Americans lack broadband access. “People who lack digital access, or don’t speak English…or know how to navigate or work with computers are unable to use that service and then don’t have access to the vaccines because they just don’t know how to get to them,” Jirmanus, an affiliate of the FXB Center for Health and Human Rights at Harvard and a member of The People’s CDC explains. She sees this issue frequently when working with immigrant communities in Massachusetts. “You really have to meet people where they’re at, and that means physically where they’re at.”
Equitable solutions
Grassroots and advocacy organizations like PTF have been filling a lot of the holes left by spotty federal policy. “In many ways this collective care has been as important as our gains to access the vaccine itself,” says Spira, the PTF co-founder.
PTF facilitates peer-to-peer networks of parents that offer support to each other. At least one parent in the group has crowdsourced information on locations that are providing vaccines for the very young and created a spreadsheet displaying vaccine locations. “It is incredible to me still that this vacuum of information and support exists, and it took a totally grassroots and volunteer effort of parents and physicians to try and respond to this need.” says Spira.
Kass, who is also affiliated with PTF, has been vaccinating any child who comes to his independent practice, regardless of whether they’re one of his patients or have insurance. “I think putting everything on retail pharmacies is not appropriate. By the time the kids' vaccines were released, all of our mass vaccination sites had been taken down.” A big way to help parents and pediatricians would be to allow mixing and matching. Any child who has had the full Pfizer series has had to forgo a bivalent booster.
“I think getting those first two or three doses into kids should still be a priority, and I don’t want to lose sight of all that,” states Renton, the researcher at Ariadne Labs. Through the vaccine equity planner, he has been trying to see if there are places where mobile clinics can go to improve access. Renton continues to work with local and state planners to aid in vaccine planning. “I think any way we can make that process a lot easier…will go a long way into building vaccine confidence and getting people vaccinated,” Renton says.
Michelle Baltes-Breitwisch, a pharmacist, and her two-year-old daughter, Charlee, live in Iowa. Her husband had to drive four hours roundtrip to get the boosters for Charlee.
Michelle Baltes-Breitwisch
Other changes need to come from the CDC. Even though the CDC “has this historic reputation and a mission of valuing equity and promoting health,” Jirmanus says, “they’re really failing. The emphasis on personal responsibility is leaving a lot of people behind.” She believes another avenue for more equitable access is creating legislation for upgraded ventilation in indoor public spaces.
Given the gaps in state policies, federal leadership matters, Raifman says. With the FDA leaning toward a yearly COVID vaccine, an equity lens from the CDC will be even more critical. “We can have data driven approaches to using evidence based policies like mask policies, when and where they're most important,” she says. Raifman wants to see a sustainable system of vaccine delivery across the country complemented with a surge preparedness plan.
With the public health emergency ending and vaccines going to the private market sometime in 2023, it seems unlikely that vaccine access is going to improve. Now more than ever, ”We need to be able to extend to people the choice of not being infected with COVID,” Jirmanus says.
*Some names were changed for privacy reasons.
What causes aging? In a paper published last month, Dr. David Sinclair, Professor in the Department of Genetics at Harvard Medical School, reports that he and his co-authors have found the answer. Harnessing this knowledge, Dr. Sinclair was able to reverse this process, making mice younger, according to the study published in the journal Cell.
I talked with Dr. Sinclair about his new study for the latest episode of Making Sense of Science. Turning back the clock on mouse age through what’s called epigenetic reprogramming – and understanding why animals get older in the first place – are key steps toward finding therapies for healthier aging in humans. We also talked about questions that have been raised about the research.
Show links:
Dr. Sinclair's paper, published last month in Cell.
Recent pre-print paper - not yet peer reviewed - showing that mice treated with Yamanaka factors lived longer than the control group.
Dr. Sinclair's podcast.
Previous research on aging and DNA mutations.
Dr. Sinclair's book, Lifespan.
Harvard Medical School