Marielle Gross, a professor at the University of Pittsburgh, shows patients a new app that tracks how their samples are used during biomedical research.
Science has come a long way since Henrietta Lacks, a Black woman from Baltimore, succumbed to cervical cancer at age 31 in 1951 -- only eight months after her diagnosis. Since then, research involving her cancer cells has advanced scientific understanding of the human papilloma virus, polio vaccines, medications for HIV/AIDS and in vitro fertilization.
Today, the World Health Organization reports that those cells are essential in mounting a COVID-19 response. But they were commercialized without the awareness or permission of Lacks or her family, who have filed a lawsuit against a biotech company for profiting from these “HeLa” cells.
While obtaining an individual's informed consent has become standard procedure before the use of tissues in medical research, many patients still don’t know what happens to their samples. Now, a new phone-based app is aiming to change that.
Tissue donors can track what scientists do with their samples while safeguarding privacy, through a pilot program initiated in October by researchers at the Johns Hopkins Berman Institute of Bioethics and the University of Pittsburgh’s Institute for Precision Medicine. The program uses blockchain technology to offer patients this opportunity through the University of Pittsburgh's Breast Disease Research Repository, while assuring that their identities remain anonymous to investigators.
A blockchain is a digital, tamper-proof ledger of transactions duplicated and distributed across a computer system network. Whenever a transaction occurs with a patient’s sample, multiple stakeholders can track it while the owner’s identity remains encrypted. Special certificates called “nonfungible tokens,” or NFTs, represent patients’ unique samples on a trusted and widely used blockchain that reinforces transparency.
Blockchain could be used to notify people if cancer researchers discover that they have certain risk factors.
“Healthcare is very data rich, but control of that data often does not lie with the patient,” said Julius Bogdan, vice president of analytics for North America at the Healthcare Information and Management Systems Society (HIMSS), a Chicago-based global technology nonprofit. “NFTs allow for the encapsulation of a patient’s data in a digital asset controlled by the patient.” He added that this technology enables a more secure and informed method of participating in clinical and research trials.
Without this technology, de-identification of patients’ samples during biomedical research had the unintended consequence of preventing them from discovering what researchers find -- even if that data could benefit their health. A solution was urgently needed, said Marielle Gross, assistant professor of obstetrics, gynecology and reproductive science and bioethics at the University of Pittsburgh School of Medicine.
“A researcher can learn something from your bio samples or medical records that could be life-saving information for you, and they have no way to let you or your doctor know,” said Gross, who is also an affiliate assistant professor at the Berman Institute. “There’s no good reason for that to stay the way that it is.”
For instance, blockchain could be used to notify people if cancer researchers discover that they have certain risk factors. Gross estimated that less than half of breast cancer patients are tested for mutations in BRCA1 and BRCA2 — tumor suppressor genes that are important in combating cancer. With normal function, these genes help prevent breast, ovarian and other cells from proliferating in an uncontrolled manner. If researchers find mutations, it’s relevant for a patient’s and family’s follow-up care — and that’s a prime example of how this newly designed app could play a life-saving role, she said.
Liz Burton was one of the first patients at the University of Pittsburgh to opt for the app -- called de-bi, which is short for decentralized biobank -- before undergoing a mastectomy for early-stage breast cancer in November, after it was diagnosed on a routine mammogram. She often takes part in medical research and looks forward to tracking her tissues.
“Anytime there’s a scientific experiment or study, I’m quick to participate -- to advance my own wellness as well as knowledge in general,” said Burton, 49, a life insurance service representative who lives in Carnegie, Pa. “It’s my way of contributing.”
Liz Burton was one of the first patients at the University of Pittsburgh to opt for the app before undergoing a mastectomy for early-stage breast cancer.
Liz Burton
The pilot program raises the issue of what investigators may owe study participants, especially since certain populations, such as Black and indigenous peoples, historically were not treated in an ethical manner for scientific purposes. “It’s a truly laudable effort,” Tamar Schiff, a postdoctoral fellow in medical ethics at New York University’s Grossman School of Medicine, said of the endeavor. “Research participants are beautifully altruistic.”
Lauren Sankary, a bioethicist and associate director of the neuroethics program at Cleveland Clinic, agrees that the pilot program provides increased transparency for study participants regarding how scientists use their tissues while acknowledging individuals’ contributions to research.
However, she added, “it may require researchers to develop a process for ongoing communication to be responsive to additional input from research participants.”
Peter H. Schwartz, professor of medicine and director of Indiana University’s Center for Bioethics in Indianapolis, said the program is promising, but he wonders what will happen if a patient has concerns about a particular research project involving their tissues.
“I can imagine a situation where a patient objects to their sample being used for some disease they’ve never heard about, or which carries some kind of stigma like a mental illness,” Schwartz said, noting that researchers would have to evaluate how to react. “There’s no simple answer to those questions, but the technology has to be assessed with an eye to the problems it could raise.”
To truly make a difference, blockchain must enable broad consent from patients, not just de-identification.
As a result, researchers may need to factor in how much information to share with patients and how to explain it, Schiff said. There are also concerns that in tracking their samples, patients could tell others what they learned before researchers are ready to publicly release this information. However, Bogdan, the vice president of the HIMSS nonprofit, believes only a minimal study identifier would be stored in an NFT, not patient data, research results or any type of proprietary trial information.
Some patients may be confused by blockchain and reluctant to embrace it. “The complexity of NFTs may prevent the average citizen from capitalizing on their potential or vendors willing to participate in the blockchain network,” Bogdan said. “Blockchain technology is also quite costly in terms of computational power and energy consumption, contributing to greenhouse gas emissions and climate change.”
In addition, this nascent, groundbreaking technology is immature and vulnerable to data security flaws, disputes over intellectual property rights and privacy issues, though it does offer baseline protections to maintain confidentiality. To truly make a difference, blockchain must enable broad consent from patients, not just de-identification, said Robyn Shapiro, a bioethicist and founding attorney at Health Sciences Law Group near Milwaukee.
The Henrietta Lacks story is a prime example, Shapiro noted. During her treatment for cervical cancer at Johns Hopkins, Lacks’s tissue was de-identified (albeit not entirely, because her cell line, HeLa, bore her initials). After her death, those cells were replicated and distributed for important and lucrative research and product development purposes without her knowledge or consent.
Nonetheless, Shapiro thinks that the initiative by the University of Pittsburgh and Johns Hopkins has potential to solve some ethical challenges involved in research use of biospecimens. “Compared to the system that allowed Lacks’s cells to be used without her permission, Shapiro said, “blockchain technology using nonfungible tokens that allow patients to follow their samples may enhance transparency, accountability and respect for persons who contribute their tissue and clinical data for research.”
Read more about laws that have prevented people from the rights to their own cells.
Theo, an 18-month-old in rural Nebraska, walks with his father in their backyard. For many toddlers, the barriers to accessing COVID-19 vaccines are many, such as few locations giving vaccines to very young children.
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.
Last month, a paper published in Cell by Harvard biologist David Sinclair explored root cause of aging, as well as examining whether this process can be controlled. We talked with Dr. Sinclair about this new 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