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Why preclinical research models must reflect diverse populations

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A new report calls out the dire need for diversity in human cell lines. piranka/Getty Images
  • In a new report, researchers cite a dire need to increase diversity in preclinical research using human cell lines (HCL). Currently, some 95% of commonly used cell lines come from people of European descent.
  • The authors explain that African Americans and other groups are under-represented in preclinical research and are often discriminated against by the medical system.
  • To fix this systemic problem, the authors write that researchers must regain the trust of previously marginalized populations to encourage people of more diverse genetic backgrounds to contribute to the development of more diverse cell lines.
  • Researchers must also consciously prioritize factors such as sex and genetic ancestry representation over ease of accessibility or the cost of a cell line.

The Black Lives Matter movement has encouraged some researchers in the biomedical community to focus on the under-representation of Black adults and other groups in medical study populations.

This is a significant problem, given that people of certain racial or ethnic backgrounds experience some conditions differently or at different rates. For example, African American men are 2.5 times more likely to die from prostate cancer than white American men. However, 97% of the human prostate cell lines made by major medical research supplies are of white European origin.

These compounding factors, such as someone’s ethnicity, race, sex, or ancestral genetic origin, are widely excluded from most preclinical and clinical research. This means that researchers are often developing treatments that may not work for all groups of people.

This situation underserves large groups of people and leads to a significant waste of time, money, and resources. It can also increase the risk that some people may be harmed by taking medications that have not received sufficient testing in their specific population.

Health inequities affect all of us differently. Visit our dedicated hub for an in-depth look at social disparities in health and what we can do to correct them.

This is why two researchers, Dr. Amanda Capes-Davis with the Children’s Medical Research Institute (CMRI) in Sydney, Australia, and Dr. Sophie Zaaijer, who has affiliations with Cornell Tech, New York, decided to create a report alerting biologists and other stakeholders of the importance of conscious decision-making when selecting cell lines for research.

Cell lines are grown from a single cell taken from living tissue. Scientists grow them outside of the body in a laboratory under controlled conditions and produce a population of cells with the same genetic make-up that can grow over a long period.

The new report, which appears in the journal Cell, also outlines ways to address this systemic issue of under-representation by proposing a simple action plan.

If widely adopted, the authors’ proposed methods could help more researchers consciously consider sex and genetic ancestry factors when choosing cell lines to study. In turn, this could help improve the impact and efficacy of preclinical and clinical research, which could help create treatments and procedures that benefit all populations.

Historically, the predominantly white medical and research community has ‘earned’ the mistrust of groups they have systematically marginalized and discriminated against, such as African Americans. The famous cases of Henrietta Lacks or the 1930s Tuskegee Institute syphilis trials are only two of the more prominent examples of such discrimination and abuse.

This distrust, in addition to reduced access to healthcare, discrimination, and other socioeconomic factors, is likely responsible for the under-representation of African Americans and other groups in many areas of medical research.

The authors write that, historically, when scientists first developed cell lines, they were geographically restricted to certain locations, and these geographical disparities were perpetuated and exacerbated over the years. Currently, Africa comprises 54 countries and 1.3 billion people, but scientists only use about 73 human cell lines from African American people and those of African descent. For comparison, Europe consists of 44 countries and 0.7 billion people, but 867 cell lines represent people of European descent.

Furthermore, the authors write that the few cell lines of African origin that we do have were obtained, historically, without consent and do not reflect the rich genetic diversity of African populations. To illustrate this point, Zaaijer and Capes-Davis use the example of African-American Henrietta Lacks, who provided, unbeknown to her, “The first human [cell line], HeLa” in 1951.

“The resulting HeLa [cell line] is responsible for many advances in biomedical research,” the authors write, but “a single [cell line] cannot be used in isolation as a model for the rich genetic diversity in the African community.”

Medical News Today also spoke with Dr. Simone Badal, who was not involved in this research, but who recently co-authored a paper calling for the need for cell lines that represent more diverse ethnic backgrounds for prostate cancer research. She said:

“98% of prostate cancer cell lines are Caucasian in origin, and all the popularly used ones are Caucasian. For breast [cancer], more than 80% are Caucasian in origin.”

Badal said she believes this has led to poorer treatment options for Black men and women with these cancers.

When asked why this issue has persisted for so long, Badal said it has potentially persisted because of a lack of attention.

“As to why this was the case to begin with, perhaps, the case with George Floyd permeates scientific research as well,” she said.

The authors of the new paper praise several projects underway worldwide tackling the issue of ancestral genetic diversity in preclinical research.

The Human Heredity and Health in African Consortium is working to increase genetic information about African populations. The Consortium’s datasets represent 426 people from 50 ethnolinguistic groups across 13 African countries that have helped discover more than 3 million genetic variants so far; some linked to disease susceptibility and outcomes.

The National Institute of Health (NIH)’s “All of Us” project also aims to monitor genetic info from millions of people from mixed, diverse backgrounds in the United States. The New York Genome Center (NYGC) is also running a large project called Polyethnic-1000 to improve research in cancer risk, treatment response, and tumor biology in ethnically diverse groups, using data from residents of New York City.

Projects such as these can help create new, more genetically diverse cell lines, improving the options available to researchers and the applicability of their findings.

The authors write that researchers must make more genetically conscious decisions throughout the research process.

Currently, the authors write that researchers consider several factors when selecting an appropriate set of HCLs for a study, including:

  • tissue type
  • presence of a certain phenotype
  • how easy it is to culture or access
  • whether other researchers use it for similar uses
  • how cheap it is
  • funding for different cell lines

The authors conclude that to improve the diversity of future cellular preclinical work, researchers must consider the genetic ancestry and sex of cell lines they use and publish them in the main text of the study.

“Awareness is created by visibility,” said Dr. Zaaijer, co-author of the report in reply to questions from Medical News Today.

“When no one publishes the ancestral origin of a cell line in the methods section of scientific manuscripts – it will not be on the radar of its scientific readership.”

The authors add that it is also important to ensure cell line genetic information is authentic or accurately matches the genetic ancestry it claims to. In a 2019 study, Caucasian cell lines were authentic 97% of the time but, Black and African American cell lines were not always described properly.

To select the most appropriate cell line, the authors write, researchers should start by creating a “wish list” of all the available cell lines that may suit their research question. They then advise researchers to record key biological metadata (KBM) of cell lines, using genetic tools to account for missing or historical information.

They also suggest that researchers publish the accompanying KBM and their reasoning for having chosen the cell lines they did.

A lack of standard genetic testing has led to a lack of KBM for certain cell lines. The authors suggest that the researchers should obtain the data by using genetic genotyping techniques in these cases.

Most of these changes are easy to implement and incur no additional costs.

What may be more difficult and costly is the work it will take to regain the trust of historically marginalized groups. The authors cite positive projects currently underway, such as work by advocacy groups to engage local communities in research. It will also be imperative to establish strong and open lines of communication between communities and researchers to identify barriers and mitigate them.

Without all of these changes, advances in personalized medicine will be severely limited, the authors write. Personalized medicine involves factoring an individual’s genetic factors into decisions around treatment, diagnosis, and disease prevention.

But if these changes take hold on a large scale in the medical research community, they could help improve disease prognosis, treatment, and outlook for billions of people otherwise excluded from traditional preclinical models.

“We hope to see the emergence of large cell line panels that represent the numerous human populations equally,” Dr. Zaaijer told MNT.

“We [also] hope preclinical scientific discoveries will be made that illuminate if and how specific human populations can be treated more effectively.”

Dr. Sam Oh, from the Department of Medicine at the University of California, San Francisco, was not involved in the current research but has authored many studies exploring the need for increased diversity in medical and genetic research. When approached by MNT to comment on the new paper, he echoed these sentiments:

“The authors [of the new paper] shine the spotlight on a long-standing issue that is important not only for scientific discovery but also for equity […]. Diversity is important because studying cell lines from diverse ancestries leads to a broader and better understanding of the biology involved — and, therefore, creates increased opportunities for scientific discovery.”

“Diversifying cell line ancestries also leads to better global representation: 76% of the world’s population live in Africa and Asia but are woefully underrepresented in biomedical science. We shouldn’t limit our discovery potential by focusing on a small slice of the genetic diversity pie.”

– Dr. Sam Oh

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