Marielle Gross, a professor at the University of Pittsburgh, shows patients a new app that tracks how their samples are used during biomedical research.
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.
Peanut allergies affect about a million children in the U.S., and most never outgrow them. Luckily, some promising remedies are in the works.
Typically, people with peanut allergies try to completely avoid them and carry an adrenaline autoinjector like an EpiPen in case of emergencies. This constant vigilance is very stressful, particularly for parents with young children.
“The search for a peanut allergy ‘cure’ has been a vigorous one,” says Claudia Gray, a pediatrician and allergist at Vincent Pallotti Hospital in Cape Town, South Africa. The closest thing to a solution so far, she says, is the process of desensitization, which exposes the patient to gradually increasing doses of peanut allergen to build up a tolerance. The most common type of desensitization is oral immunotherapy, where patients ingest small quantities of peanut powder. It has been effective but there is a risk of anaphylaxis since it involves swallowing the allergen.
"By the end of the trial, my son tolerated approximately 1.5 peanuts," Sharon Wong says.
DBV Technologies, a company based in Montrouge, France has created a skin patch to address this problem. The Viaskin Patch contains a much lower amount of peanut allergen than oral immunotherapy and delivers it through the skin to slowly increase tolerance. This decreases the risk of anaphylaxis.
Wong heard about the peanut patch and wanted her son to take part in an early phase 2 trial for 4-to-11-year-olds.
“We felt that participating in DBV’s peanut patch trial would give him the best chance at desensitization or at least increase his tolerance from a speck of peanut to a peanut,” Wong says. “The daily routine was quite simple, remove the old patch and then apply a new one. By the end of the trial, he tolerated approximately 1.5 peanuts.”
How it works
For DBV Technologies, it all began when pediatric gastroenterologist Pierre-Henri Benhamou teamed up with fellow professor of gastroenterology Christopher Dupont and his brother, engineer Bertrand Dupont. Together they created a more effective skin patch to detect when babies have allergies to cow's milk. Then they realized that the patch could actually be used to treat allergies by promoting tolerance. They decided to focus on peanut allergies first as the more dangerous.
The Viaskin patch utilizes the fact that the skin can promote tolerance to external stimuli. The skin is the body’s first defense. Controlling the extent of the immune response is crucial for the skin. So it has defense mechanisms against external stimuli and can promote tolerance.
The patch consists of an adhesive foam ring with a plastic film on top. A small amount of peanut protein is placed in the center. The adhesive ring is attached to the back of the patient's body. The peanut protein sits above the skin but does not directly touch it. As the patient sweats, water droplets on the inside of the film dissolve the peanut protein, which is then absorbed into the skin.
The peanut protein is then captured by skin cells called Langerhans cells. They play an important role in getting the immune system to tolerate certain external stimuli. Langerhans cells take the peanut protein to lymph nodes which activate T regulatory cells. T regulatory cells suppress the allergic response.
A different patch is applied to the skin every day to increase tolerance. It’s both easy to use and convenient.
“The DBV approach uses much smaller amounts than oral immunotherapy and works through the skin significantly reducing the risk of allergic reactions,” says Edwin H. Kim, the division chief of Pediatric Allergy and Immunology at the University of North Carolina, U.S., and one of the principal investigators of Viaskin’s clinical trials. “By not going through the mouth, the patch also avoids the taste and texture issues. Finally, the ability to apply a patch and immediately go about your day may be very attractive to very busy patients and families.”
Brandon Wong displaying origami figures he folded at an Origami Convention in 2022
Sharon Wong
Clinical trials
Results from DBV's phase 3 trial in children ages 1 to 3 show its potential. For a positive result, patients who could not tolerate 10 milligrams or less of peanut protein had to be able to manage 300 mg or more after 12 months. Toddlers who could already tolerate more than 10 mg needed to be able to manage 1000 mg or more. In the end, 67 percent of subjects using the Viaskin patch met the target as compared to 33 percent of patients taking the placebo dose.
“The Viaskin peanut patch has been studied in several clinical trials to date with promising results,” says Suzanne M. Barshow, assistant professor of medicine in allergy and asthma research at Stanford University School of Medicine in the U.S. “The data shows that it is safe and well-tolerated. Compared to oral immunotherapy, treatment with the patch results in fewer side effects but appears to be less effective in achieving desensitization.”
The primary reason the patch is less potent is that oral immunotherapy uses a larger amount of the allergen. Additionally, absorption of the peanut protein into the skin could be erratic.
Gray also highlights that there is some tradeoff between risk and efficacy.
“The peanut patch is an exciting advance but not as effective as the oral route,” Gray says. “For those patients who are very sensitive to orally ingested peanut in oral immunotherapy or have an aversion to oral peanut, it has a use. So, essentially, the form of immunotherapy will have to be tailored to each patient.” Having different forms such as the Viaskin patch which is applied to the skin or pills that patients can swallow or dissolve under the tongue is helpful.
The hope is that the patch’s efficacy will increase over time. The team is currently running a follow-up trial, where the same patients continue using the patch.
“It is a very important study to show whether the benefit achieved after 12 months on the patch stays stable or hopefully continues to grow with longer duration,” says Kim, who is an investigator in this follow-up trial.
"My son now attends university in Massachusetts, lives on-campus, and eats dorm food. He has so much more freedom," Wong says.
The team is further ahead in the phase 3 follow-up trial for 4-to-11-year-olds. The initial phase 3 trial was not as successful as the trial for kids between one and three. The patch enabled patients to tolerate more peanuts but there was not a significant enough difference compared to the placebo group to be definitive. The follow-up trial showed greater potency. It suggests that the longer patients are on the patch, the stronger its effects.
They’re also testing if making the patch bigger, changing the shape and extending the minimum time it’s worn can improve its benefits in a trial for a new group of 4-to-11 year-olds.
The future
DBV Technologies is using the skin patch to treat cow’s milk allergies in children ages 1 to 17. They’re currently in phase 2 trials.
As for the peanut allergy trials in toddlers, the hope is to see more efficacy soon.
For Wong’s son who took part in the earlier phase 2 trial for 4-to-11-year-olds, the patch has transformed his life.
“My son continues to maintain his peanut tolerance and is not affected by peanut dust in the air or cross-contact,” Wong says. ”He attends university in Massachusetts, lives on-campus, and eats dorm food. He still carries an EpiPen but has so much more freedom than before his clinical trial. We will always be grateful.”