A HeLa Lawsuit Is Over. The Ethics Debate Over Human Samples Isn't.

In February, the family of Henrietta Lacks settled a lawsuit with biotechnology company Novartis regarding the company’s use of HeLa cells, the immortalized cell line that came from Lacks’ cancer cells. In 1951, Lacks had a cervical tumor removed, and her doctor passed some of these cells on to a researcher trying to grow cells in culture. At the time, this practice was common and legal. The ethical requirement for informed consent, which includes researchers asking patients permission to take samples and informing them about the research being done on those samples, wasn’t formalized until 1991.

In the mid 1970s, researchers contacted Lack’s surviving relatives to conduct genetic testing to compare their genotypes to that of the HeLa cells.¹ “It became clear that the family was not aware that her cells had been growing in culture,” said Christine Grady, a bioethicist at Georgetown University.

At this same time, the family learned about the innovations and resulting profits that were made from her tissues without their knowledge. “They were also in a situation where some of them were having difficulty accessing the healthcare that they needed, and that felt very unfair. The world was making profits off of their mother's cells or their grandmother's cells, and they were struggling to get healthcare,” Grady said. In response, the family filed multiple lawsuits against pharmaceutical companies for improperly profiting from her cells. The first was settled in 2023.

As the Lacks family continues to contend with the ripples of these long-lived samples, researchers also grapple with the complex and sometimes ambiguous ethics that attempt to guide more fair and thoughtful research. From consent and data sharing to ethical science representation, scientists, ethicists, and communities need to work together to move research forward for the public good.

Human Research Must Include Informed Consent, Not Just Consent

At the heart of the HeLa cell controversy is the absence of informed consent, which involves not only getting people’s permission to participate in or donate samples for a research study but also telling them about the goals and potential risks and benefits involved in the research. Erica Jonlin, a regulatory manager at the University of Washington, helps researchers design experiments involving human subjects or their samples, including speaking with research participants to have informed consent discussions.

“[Basic science researchers are not] used to really considering the issues of how you get human specimens and all the bioethical issues with respect to these specimens,” Jonlin said. For example, as was the case for Lacks, participants’ cells and tissues may be immortalized and sequenced, leading to privacy concerns for the individuals or their families.

Making sure that people not only agree to share their samples but also understand the intended and potential use, Jonlin said, is critical. “A consent form might say something, but it's not informed consent if there wasn't a discussion and…it wasn't explained to them all the things that might be done,” she said.

A famous example of the importance of proper informed consent comes from a tribe of American Indians, called the Havasupai. In 1989, tribal leaders reached out to anthropologist John Martin at Arizona State University (ASU) about studying the high incidence of diabetes in their community. Martin invited genetics researcher Therese Markow, also at ASU at the time, and together they collected blood from the tribe members. However, the language of the consent form opened the door for the samples to be used for studying other topics beyond the scope of the project.

Decades later, one tribal member who had donated a sample for this research was attending a dissertation defense at ASU that discussed results about migration studies done with her tribe’s samples.² The Havasupai community learned that their samples had been shared with other researchers to conduct studies on schizophrenia, inbreeding, and the tribe’s origins, all of which were seen as taboo subjects in their culture.

“It was highly disrespectful. And if they had realized that, they would never have given their consent. So again, part of the problem is the consent wasn't informed,” Jonlin said.

Additionally, this example underlined how researchers who receive human samples from their colleagues must confirm that they obtained the proper informed consent before the new team uses them. Jonlin noted that it’s important for scientists planning to conduct research with human samples to determine how they will keep track of the samples and the corresponding informed consent information to ensure proper storage, management, hand offs. Failure to do so, Jonlin said, can have far-reaching and damaging consequences.

In 2004, the Havasupai tribal members sued ASU for misusing the samples and providing them with improper consent details. Eventually, the groups settled, and the tribe received financial compensation, education and economic development support for their community, and the return of the remaining samples.

“In the end, the university lost out. They lost specimens. They lost their reputation. They lost money,” Jonlin said. But the fallout from the ethical violations of the Havasupai study also impacted research with this tribe, as the group ceased collaborating with scientists. Loss of a communities’ participation in research can have long-reaching effects on understanding unique populations and emphasizes the importance of proper ethics in research.

Follow up studies on researcher perspectives of this incident indicated that most scientists felt that working on genetics projects with native communities in the future would require them to either obtain broad consent for sample usage or exclude these groups from research altogether.^3,4 This highlights how ethical considerations in research still have room for improvement and consideration.

Leftover Samples and “Broad Consent” Opens More Ethical Conundrums

Typically in a consent form, researchers outline the precise samples they want to collect, the purpose for them, and how these specimens will be used. But research projects often change as technology advances or results steer scientists in new directions. In these cases, Jonlin said that many institutional review boards require researchers to recontact donors and reconsent them.

This can prove difficult: People move, die, or become otherwise unreachable. Their information can also get inadvertently separated from their samples. “In some cases, you really shouldn't do the research on the specimens, unless you do recontact and reconsent,” Jonlin said.

To address these issues and make research participation a more iterative process, some ethics experts have proposed a model of dynamic consent, in which donors can stay electronically connected to the research being performed using their samples, which allows them to indicate and update their consent preferences.^5,6 Alternatively, other ethicists have proposed a completely new paradigm in how to approach consent, where instead of individuals agreeing to context-specific studies, they give permission for responsible groups to use their samples within an agreed upon framework.^7,8

Yet researchers also obtain samples outside of dedicated research projects, often in the form of leftover clinical samples. These create a gray area in research. This material can supply researchers with less selection-biased specimen pools and provide access to samples with unique conditions that can be hard to obtain in traditional studies.⁹ These samples are deidentified, meaning that a third party removes the individual’s name and other specific information from the specimen before it goes to researchers so that any findings from the donor’s sample cannot be traced back to them. Because of this, the US federal government doesn’t require informed consent for these samples to be used for research. Anonymized samples have also traditionally been exempted from consent requirements in many European countries.

Some hospitals or other medical centers will require people to fill out a form that gives broad consent for this donation, but typically people often won’t know what their leftover specimen may be used for. Broad consent is also the current standard for many biobanks, where samples are anonymized, though some have also adopted dynamic consent models.

Some surveys suggest that, overall, people don’t want to be contacted about every potential new use of a past specimen. Yet not everyone agrees that this is the most appropriate approach since there may be some types of research, like cloning, that people object to their samples being used for.^9,10 “So, it’s really hard to get a handle on that,” Grady said.

Jonlin also said that broad consent can become a problem if researchers end up sequencing the samples in their study and want to publish their findings. Most journals require genomic sequences to be available in a repository, but many databases insist that researchers provide the informed consent documents for those sequences as well.

With advancements in genomic technologies and more people using genome services to study ancestry, there are also increasing risks for individuals to be reidentified. Although this currently takes a significant amount of effort to do, Grady said, “There are people who argue that deidentification is never complete.” The increasing amount of patient or participant data available is also posing challenges as governments update data privacy laws, creating the need to consider new approaches for using human samples in research.¹¹

From a regulatory perspective, Jonlin added that broad consent is too vague, but the potential identification risks depend on what research is being done. Some studies, like spatial genomics or biomarker exploration in tumors, pose little chance of privacy invasion. However, wherever a researcher intends to conduct and then publish a specimen’s genomic sequence creates an opportunity to expose an individual. “Their identifiable information is out there, and the relatives are out there, and so someone needs to give informed consent about that,” she said.

This exact situation came to pass when researchers published the genomic sequence of HeLa cells in 2013, leading to an outcry from scientists and bioethicists.¹² The researchers eventually contacted Lacks’s descendants to talk about how to resolve the situation and also removed the sequence from the internet. The family members worked with scientists at the National Institutes of Health (NIH) at the time to create a system where HeLa sequences could be uploaded to the NIH’s genome database, but both NIH scientists and Lacks family members would review all requests to use the sequences. While this solution addressed the immediate concerns from the initial publication, the agreement only pertained to grants funded by the NIH and sequences being uploaded to the institution’s database.¹³

Beyond adding the highly popularized HeLa sequences, many researchers upload genomic sequences from other human samples to this NIH database as part of the data sharing plans required by their grants. To upload a sequence, researchers have to submit the study information, including the appropriate consent forms, to the database. These sequences are not publicly available; instead, scientists must request access to the datasets. The database committee then checks their credentials and the validity of their research before approving the database’s use.

But Jantina de Vries, an ethicist at the University of Cape Town, pointed out that no system is foolproof. “The landscape is…forever changing,” she said. As new technology gives researchers more ways to collect information, the chance of unintentionally exposing and reidentifying individuals increases, creating ethical conflicts for researchers in protecting patient privacy while also fulfilling their obligations to share their data.¹⁴ “But scientists are constantly innovating to think about and reduce the risk of harm whilst opening up the possibility to do good with data.” Some of these strategies include using blockchain systems to protect privacy or introducing federated systems that allow researchers to make inquiries about data sets without accessing the data itself.^15,16

At the same time, though, de Vries said that researchers and ethics boards may be placing too much focus on how people could use genomic data to cause harm. “The protection against the nebulous harm…has impeded the scientific value that sharing would have had and hasn’t actually protected people all that well,” she said. “So rather than say we must protect people from harm, what we must do is recognize that when people participate in studies, they usually do that because they want to help.”

de Vries said that if scientists assume altruism is the leading reason people participate in research, then they should try to ensure that studies and the data that comes from them can have the greatest positive effect on the world. For example, some ethicists have called for implementing models of data solidarity, in which data is collectively owned and controlled.¹⁷ This may also include incorporating financial incentives against using data that does pose individual or societal risk while encouraging greater support for high-value, low-risk data use.

de Vries said, “Maybe it's not just about protections against harm but maybe it is much more actively about thinking about how our science and technologies support all people to live right in the world.”

Representative Research is an Ethical Obligation

While the intention to protect people’s privacy is well-meaning, de Vries said that researchers also have an ethical responsibility to design studies that will help individuals and their communities, especially those that have been excluded or exploited in health research before. “Consent in itself doesn't make a study ethical. It also doesn't mean that even if you get consent, people are no longer exploited,” she said.

For example, beyond the Havasupai’s lawsuit, other Indigenous communities reported feeling exploited when approached by scientists to contribute samples to the Human Genome Diversity Project.¹⁸ After taking samples from members of the community, researchers made no attempt to follow up with them to share results or other resources. de Vries emphasized that, for research involving vulnerable communities, the study must also include community engagement, considering their values, interests, and communicating important research findings where possible.

Taking steps to engage these underrepresented communities is important because making research representative of the full diversity of the human population is also an ethical obligation. Science history contains many unfortunate examples where populations were intentionally excluded from studies and resources, leaving them underrepresented in research needed to guide medical decisions, which continue to have consequences for minority communities today.

One important example lies in genetic studies of cardiomyopathy. As these studies yielded more insights into risks of variants for cardiomyopathy, physicians would use this information to guide clinical diagnostics and recommendations.^19,20 This included advising against participation in physical sports or suggesting the implantation of a pacemaker.

Yet when researchers assessed these variants against diverse populations in one study, they found that many of these variations do not pose the same risk in people of African descent. The original studies missed this because they had not included a representative sample of this population.²¹

Poor representation in research studies like these leads to misinformed clinical recommendations, which in some cases included otherwise unneeded surgery. “That was unnecessary harm done to a community simply because they were not involved in the research,” de Vries said.

Yet, while there is a clear, medically important reason to be included in these types of research, many people from historically marginalized communities refrain from participating in scientific studies. Surveys show that groups underrepresented in science, including Black people, women, and poor communities, have more distrust of research.^22,23 Meanwhile, other studies indicated that many communities were willing to participate in research with lack of access being a larger deterrent.^24,25 “We have a long way to go. We have a lot of work to do to build trust in these populations,” Jonlin said.

Scientists and research societies have also taken note of this need for engagement and representation. In the field of cancer research, leading organization members outlined strategies to study and engage underserved communities to improve cancer detection and treatment intervention in minority populations.²⁶ De Vries, in collaboration with the African communities she works with, considers what type of research will support marginalized communities’ agency and dignity and how to make that work accessible. She and her colleagues previously identified how focusing on principles of solidarity, reciprocity, and inclusivity, among others central to the values of many African communities could successfully guide genomics research in these populations.²⁷

Dovetailing with this, bioethics researchers have shown that while many Indigenous people want to participate in research, these studies must be done in collaboration with the community to protect their interests and concerns, including efforts to avoid stigmatization, increase research transparency, and respecting cultural practices and history.^18,28

Jonlin added that the research community must also be diverse so that individuals from these backgrounds can speak directly to scientists who are in their own communities, building connections and trust. For example, churches and community figures were critical in helping convince Black populations to participate in vaccine trials during the COVID-19 pandemic and eventually receiving the shot.^29,30 Researchers have also found that Indigenous communities are more comfortable participating in research that is led by a community member.¹⁸ This was true of other minority groups as well.^22,23,31

Above all, Jonlin and de Vries emphasized that researchers must give back to the communities they include in their studies. This could be in the form of sharing research findings, if possible, but it could also be supporting the community through development opportunities.

Ethics Are the Foundation of Research

Since the time of Lacks and the creation of HeLa cells, several other ethical debates have arisen: some similar to Lacks’s story, others distinct. Each time, researchers, ethicists, lawyers, and the public have redefined what research should look like and how it should be done.

In the 1980s, one cancer patient learned that researchers had taken samples of his tumor and used them to generate biotechnology tools that the university patented. Similar to lawsuits from the Lacks estate, the patient sued on the grounds that he should be entitled to a share of the profits since the cells came from his body. He also argued he had not been properly informed of the use of his resected tumor for research and felt deceived.

While the court eventually agreed that the researchers had not received proper consent, it disagreed that the patient as the source of the cells was owed profits, stating that donors do not make intellectual contributions to the patented technology with their samples. In contrast, if donors or relatives working on their behalf contribute more than just tissues, such as necessary financial support or other resources, another court case agreed that these parties would be eligible for monetary compensation. These cases set today’s precedent for the outcomes of research from human sample donations.

Today, the ethical landscape is vastly different from Lacks’s time. Yet, the ethicists all agreed that there is still the potential for a similar scenario to unfold again, especially given the profit-driven focus of the health and medicine sectors. As research continues to advance technology and explore how to best serve communities, these conversations will continue.

“We need to have ethical discussions, at the very least, and not just plow ahead and move forward and just do whatever we want because it seems expedient. [It] seems like a good idea. It seems like it'll make us rich,” Jonlin said. “Ethics is integral in every kind of research study. And in the end, it's taxpayer dollars. It's good governance of money. It's paying back the society that pays for the research. It's trust.”