In this research piece, we delve into the human cell lines (HeLa and SiHa) that have made contemporary advancements in cervical cancer research, and potential elimination, possible, including the critical work we do at Teal Health to bring you at-home cervical cancer screening. We explain the significance of these cell lines and discuss the women, particularly Henrietta Lacks, without whom these cells and the discoveries they enabled would not exist. Importantly, we uncover a history of bioethical harms that often surrounded how clinical research was practiced in the United States. We illuminate how the HeLa and SiHa cell lines are at the foundation of our clinical studies and detail our efforts to conduct inclusive, ethical research that closes the cervical cancer screening gap.

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What are the HeLa and SiHa Cell Lines?

Cervical cancer that is diagnosed at an early stage, when it is still localized, can be cured almost 91% of the time. This promising cure rate would not have been achieved without the critical contributions of the HeLa and SiHa cell lines and the women behind them. Over 95% of cervical cancers are caused by untreated, persistent infections of high-risk Human Papillomavirus (HPV) types. In particular, there are two HPV types – HPV16 and HPV18 – that are responsible for approximately 70% of cervical cancers. The HeLa cell line has enabled scientists to understand the role of HPV18, while the SiHa cell line illuminated HPV16 in cervical cancer research.

These cell lines are critical to contemporary medical research because they allow scientists to understand how human cells behave (e.g., when exposed to toxins, radiation, infection, anti-cancer drugs) without experimenting on humans themselves. Notably, both cell lines have enabled the development of vaccines including the HPV vaccine, which is very effective at protecting against HPV infections that can lead to cervical cancer (the Centers for Disease Control note almost 100% efficacy in some cases).  

The HeLa cells are named after Henrietta Lacks, from whom they were taken without consent in 1951 as she sought treatment for cervical cancer at Johns Hopkins Hospital. Later, around the mid-1970s, the SiHa cell line was derived from a 55-year-old Japanese patient with squamous cell carcinoma. Less is known about the woman behind the SiHa cells due to patient privacy and consent measures that had been established at the time. These protections were put into place following the bioethical violations that took place when Henrietta’s cells were taken without her knowledge or consent decades earlier.

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HeLa cells are considered the oldest and most commonly used cell line in scientific research. In addition to informing numerous advancements in cancer research and treatment, HeLa cells laid the foundation for drug development (including the polio vaccine), provided insight into how X-rays impact humans, and informed our understanding of a range of medical conditions from salmonella to HIV and tuberculosis. Particularly unique to the HeLa cells is their ability to divide and multiply indefinitely under controlled laboratory conditions. 

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Genetically, HeLa cells have an active version of telomerase, which prevents telomere shortening. A telomere is a repetitive DNA sequence located at the ends of chromosomes. Each time a cell divides, telomeres shorten, which eventually limits the number of times a cell can replicate, leading to cell aging. However, without telomere shortening, HeLa cells are ‘immortal.’ The HeLa cells were one of the first cell cultures ever to be created and have since been instrumental in cell culture techniques that make modern biomedicine possible. 

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The SiHa cell line, positive for HPV 16, is just as fundamental to biomedicine and research around cervical cancer development, progression, and possible treatments. These cells also multiply at a relatively fast pace, doubling every 17-21 hours. The SiHa cell line is largely used in drug development, to test the efficacy of potential cancer treatments and therapies.

Today, both the SiHa and HeLa cell lines are well established and their diverse populations are used across different laboratories (including those Teal Health relies on for our analytical analyses). These cell lines are fundamental to the research that our clinical team does in analyzing the reproducibility and stability of at-home self-collection methods to identify HPV 16 and HPV 18. 

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How do HPV Cell Lines Enable Teal’s Clinical Studies?

Teal Health is working to make self-collected cervical cancer screening possible at home, with consistent support from providers on our telehealth platform. We are working to expand access to life-saving screening for those who are underscreened and disproportionately impacted by cervical cancer, which includes women of color and low-income women, including those living in rural areas with less access to clinics. Our work on cervical cancer screening would not exist without HeLa and SiHa cell lines, which are foundational to Teal’s analytical testing of how the Teal Wand^TM (using FDA-approved HPV assays) facilitates accurate detection of HPV. 

HeLa and SiHa cell lines have allowed us to develop a HPV testing approach designed for at-home self-collection. Using these cell lines, we conduct rigorous analytical evaluation in a controlled laboratory setting without the variability inherent to patient samples, enabling us to assess central questions for device performance of the Teal Wand. As you can see below, at the top of the Wand is a sponge, which can be extended and retracted. This sponge is used to collect the sample for testing:

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For this sponge, we began by testing various ways to process self-collected samples in the laboratory and ultimately landed on our current ‘dry sponge’ process (i.e., not requiring a liquid preservative for transport to a laboratory), which we then used in our SELF-CERV clinical study. Notably, the dry sponge approach is optimized for at-home self-collection, and Teal Health is among the first to perfect its use. The Food and Drug Administration (FDA) acknowledged the importance of this advancement, granting Teal Health with Breakthrough Device Designation that fast-tracks the FDA review of Teal’s final study data when submitted to the Agency. 

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We also use HeLa and SiHa cell lines in our shipping stability testing. This is the process whereby we ensure that even when our samples are shipped in the mail over several days in varying conditions, the sample can still accurately detect HPV.

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Our Clinical Studies Are Designed For Women, By Women

At Teal, we also recognize and actively address the gaps in healthcare for women, much of which stems from a lack of diverse gender inclusion in clinical trials. Recent research suggests that 64% of existing medical interventions are less effective and less accessible to women. Clinical research does not equitably benefit women because researchers often fail to recruit adequate numbers of women and individuals across diverse ethnic and racial groups. In the United States, these gaps in research cost each woman four days of her life, per year.

These gaps are a part of a gendered history. In 1977, the FDA banned women of "childbearing potential" from participating in clinical research studies. This was not reversed until 1993, when the National Institutes of Health (NIH) required that women be included in clinical studies. Issues around representation persist, especially in phase I or early-stage drug trials. A recent study found that women accounted for only 29-34% of participants in industry-sponsored early-phase trials. Due to underrepresentation, women experience adverse effects from medications at twice the rate of men.

Teal Health’s clinical studies fundamentally rely on representing women and those of varying gender, racial, and ethnic identities. Teal’s SELF-CERV clinical trial included those who are aged 25-65 years old and have an intact cervix. Our participants are largely women, although there are several who identify as transgender, gender queer, or gender non-conforming. In terms of race and ethnicity, our participants are diverse and representative of the United States population. We are working to close the healthcare gap for women and people with a cervix, and the success of our research practices is grounded in inclusivity.  

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Who are the women behind the HeLa and SiHa cell lines?

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First, a Note From Teal: We recognize the unethical and inequitable manner in which Henrietta Lacks’ cells were taken and used, which reflects a history of systemic bioethical harms. In our clinical trial, all research participants provided written informed consent that was approved by an Institutional Review Board (IRB). Using patient informed consent, participants in our research studies were offered the opportunity for their sample to be used for further research, with the understanding that their participation is always voluntary.  

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Henrietta Lacks

Born in 1920 in Roanoke, Virginia, Henrietta Lacks (named Loretta Pleasant at birth), was a Black woman, a mother to five children, and a wife. Living in the era of Jim Crow, she grew up working on a tobacco farm in Virginia, and later moved to Maryland with her husband and children. In 1951, she was diagnosed with cervical cancer at age 31, after seeking care at Johns Hopkins Hospital in Baltimore. The systematic racism of this time is a pertinent factor in how Henrietta’s cancer treatment was handled, and how her cells were extracted and distributed worldwide without her knowledge or consent.

Around the time that she gave birth to her fourth child, Henrietta knew that something didn’t feel right. She complained to her close girlfriends about “a knot” inside her and would tell them that sex with her husband had become very painful. Still, she went about life as usual, and had her fifth child in late 1950. 

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It was at this point when Henrietta found unusual vaginal bleeding, which we know today to be a common symptom of cervical cancer. She felt inside her vagina, locating her cervix and finding “the knot” – a hard lump. When the lump came back negative for syphilis at her local clinic, Henrietta was sent to Johns Hopkins Gynecology Clinic in January 1951, one of the few places that would provide care to Black individuals during racial segregation.

Henrietta’s patient records at Johns Hopkins document her worsening symptoms. When Dr. Howard Jones, the gynecologist on duty, examined Henrietta, he indeed found the lump on her cervix. In his records, Dr. Jones wrote that he had never seen a cervical cancer lesion like Henrietta’s, which appeared “shiny and purple” and “bled at the slightest touch.” He remarked at how quickly the tumor had grown – only a few months prior, Henrietta had visited Johns Hopkins Hospital for her six-week postnatal appointment, and no visible cervical abnormalities were noted at the time. Yet, a biopsy now diagnosed her with “epidermoid carcinoma of the cervix, Stage I.”

There were several doctors at Johns Hopkins engaged in biomedical research when Henrietta was being treated. Among them were Dr. Richard TeLinde and Dr. Jones, who were involved in Henrietta’s care. Not only were bioethical practices around patients’ informed consent unheard of at the time, but Black individuals were systematically mistreated, exploited, and discriminated against. Medical practices were no exception to this racism. TeLinde and Jones would often use Black patients for their research needs, typically without knowledge or consent. In Dr. Jones’ words, “Hopkins, with its large indigent black population, had no dearth of clinical material.”

TeLinde gathered cells from any woman– including Henrietta– at Johns Hopkins with cervical cancer. In the 1950s, there were around 15,000 women dying each year from cervical cancer in the United States. For comparison, this number is closer to 4,000 today, in large part due to cervical cancer screening (first developed in 1941 with the Pap smear) and the HPV vaccine (made available in 2006 in the US). However, in the 1950s, there was an absence of research on how cervical cancer presents and progresses. It was assumed that invasive cancer, which had spread (i.e., metastasized), was distinct from ‘carcinoma in situ’ wherein the cancer had remained localized in its origin site. TeLinde and Jones were engaged in research to show what we know today – that localized cancer would metastasize if not appropriately treated. At the crux of their research were Henrietta’s cells, which have led to today’s practices of diagnosing and treating cancer as early as possible to limit metastasis. 

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As Henrietta came in for her cervical cancer treatment, lying unconscious on an operating table awaiting radium treatment (the contemporary standard of care), her surgeon Dr. Lawrence Wharton Jr. had been instructed by Dr. TeLinde to gather Henrietta’s cervical cells. The doctors extracted tissue from Henrietta’s tumor, as well as her nearby healthy cervical tissue, all without her awareness. This tissue was given to Dr. George Gey, the Head of Tissue Culture Research at Johns Hopkins, who had spent the past three decades trying to grow the first ‘immortal’ human cell line (where cells would continuously multiply, without depleting, as HeLa does).

When Dr. Gey realized that Henrietta’s cells would multiply indefinitely, he began sending them to any researcher around the world who asked for a sample. Her cells were sent all over the United States, and as far as India, the Netherlands, and Chile. Henrietta’s cells were sent in the mail, brought with Dr. Gey to professional meetings to distribute, and given to airplane pilots and stewards to transport in their shirt pockets. Dr. Gey and his colleagues treated Henrietta as a means for her cells, with little consideration for her as a patient. 

While her cells are the building blocks of biomedicine, especially the research on cancer and anti-cancer drugs we have today, Henrietta and her family had no knowledge that her cells had been taken during her cervical cancer treatment. Henrietta continued to undergo treatments, even as her cancer was relentlessly spreading. She complained of worsening pains and other symptoms, but doctors at Johns Hopkins did not address her concerns until it was too late. Once they finally examined her, they found that tumors had spread throughout her abdomen, bones, and labia. Henrietta died soon after in October 1951, at only 31 years old. As her family could not afford otherwise, she was buried in an unmarked grave. One could infer that a large part of the medical neglect toward Henrietta was due to her race and class.

Henrietta’s identity as the woman behind the HeLa cells was revealed without her family’s knowledge. It was not until the 1970s when her family was made aware that the HeLa cell line existed, almost 20 years after Henrietta’s passing. Many of her family members expressed feeling exploited– while Henrietta’s cells were leading to profitable discoveries, they continued to live in dire poverty.

If you want to dive deeper, here are the sources we relied on to tell Henrietta’s story:

1. The Immortal Life of Henrietta Lacks, by Rebecca Skloot
2. https://www.hopkinsmedicine.org/henrietta-lacks
3. https://osp.od.nih.gov/hela-cells/significant-research-advances-enabled-by-hela-cells/
4. https://www.biography.com/history-culture/henrietta-lacks
5. https://www.britannica.com/biography/Henrietta-Lacks
6. https://embryo.asu.edu/pages/henrietta-lacks-1920-1951

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The Woman Behind ‘SiHa’

Less is known about the woman behind SiHa, which in contemporary biomedical research is an appropriate practice to protect and uphold patient confidentiality, privacy, and consent. The SiHa cell line was isolated from a 55-year-old Japanese woman who had been diagnosed with cervical squamous cell carcinoma. The cells were taken from a biopsy the patient underwent as a part of her cervical cancer treatment. Research using the SiHa cell line first appears in the scientific literature around 1977, so it is likely these cells were derived from the patient in the years preceding.

To learn more about the SiHa cells, you can look into the sources we relied on: 

1. https://www.atcc.org/products/htb-35
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307077/
3. https://www.biocompare.com/11023-Cells-and-Microorganisms/18607705-SiHa-Cell-Line/
4. https://www.cytion.com/us/Knowledge-Hub/Cell-Line-Insights/SIHA-Cell-Line-Shedding-Light-on-Cervical-Cancer-Research/
5. https://www.embopress.org/doi/10.1038/sj.emboj.7601665
6. https://www.nature.com/articles/s41598-018-38315-7

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Acknowledging the History of Bioethical Harms

The wrongdoing against Henrietta Lacks and her family is part of a troublesome past around clinical research in the United States (e.g., The Tuskegee Experiment, Havasupai Tribe v. Arizona Board of Regents case). As in the case of creating the HeLa cell lines, this history of bioethical harms in clinical research is racialized, gendered, and disproportionately impacts those who are low-income. 

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In particular, the field of modern gynecology, including the invention of the speculum, is rooted in unethical experimentation on enslaved Black women. Dr. J. Marion Sims, often called the "father of modern gynecology," conducted experiments on enslaved Black women without using anesthesia or their consent in the 1840s. We know the names of three women Sims experimented on – Anarcha, Betsey, and Lucy – but there were numerous others. We also know that Anarcha endured around 30 operations without anesthesia. Sims did not use anesthesia on Black women, assuming that they could withstand higher amounts of pain.  

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Often, enslaved Black women were manipulated into participating in Sims’ experiments with promises that their medical concerns would be addressed. Once he ‘perfected’ his techniques on enslaved women, Sims went on to treat white women – using anesthesia. He also developed the speculum after experimentation on enslaved Black women. The ‘modern’ speculum, despite being over 150 years old, is still commonly used in gynecology (we hope the Teal Wand can offer an alternative for those who cannot, or choose not to undergo an exam using a speculum). 

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While there have been recent efforts to acknowledge the "Mothers of Gynecology," this history of medical racism has contributed to ongoing healthcare disparities, which disproportionately impact Black women (e.g., higher rates of maternal mortality and pregnancy-related complications). There are also continued racial biases in medicine, particularly around how women of color experience pain. As recently as 2016, a nationwide study in the US found that nearly half of all medical students and residents agreed that “Black people’s skin is thicker than white people’s,” assuming Black patients felt less pain.  

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More Recent Efforts to Protect Individuals Participating in Clinical Studies 

Today, it is required that those conducting biomedical research abide by strict ethical guidelines and approvals, especially around doing no harm, informed consent, patient privacy, and confidentiality.

The NIH has established strict guidelines for obtaining informed consent from research participants through an IRB, which aims to protect participants’ safety and welfare.

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As of 1993, the NIH mandates the inclusion of women and racial and ethnic minority groups in research, so that findings are applicable to diverse populations. There is also a growing movement around “data sovereignty” for marginalized populations who participate in clinical research. Further, all clinical trials are required to be registered, ensuring research transparency.

At Teal, we take these principles to protect our research participants very seriously. Teal's clinical trials are registered on ClinicalTrials.gov (NCT05669911, where WCG served as the IRB, and NCT06120205, where Advarra served as the IRB). Our nationwide clinical trial was carried out in partnership with leading healthcare organizations, and we strive to ensure our participants are both diverse and representative of the US population. 

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A Few Closing Thoughts

Teal is grateful to the women behind the HeLa and SiHa cell lines, whose contributions are at the crux of the biomedical field’s efforts on cervical cancer screening. We confront the unacceptable circumstances under which cell lines have been historically obtained, especially in the case of Henrietta Lacks. Teal Health is committed to being part of rewriting the future of women's healthcare, ensuring that the progress we contribute to is achieved through ethical, equitable, and just research practices.

The future of women's health holds potential for more equitable solutions that address the specific and unique needs women face. Teal Health's mission to bring cervical cancer screening into the home is a significant step in this direction. By providing a convenient, comfortable, private, and accessible method for at-home self-collection, we aim to remove barriers to cervical cancer screening. The Teal Wand and telehealth platform not only empower women and people with cervixes to prioritize their health, but also contribute to the broader goal of expanding access to screening and eliminating cervical cancer as a public health concern.

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