HEK293 cells are one of the most widely used platforms in biomedical science, serving as biological factories for research and drug development. They are an immortalized line of human cells, meaning they can divide and grow indefinitely in a laboratory setting. This ability, coupled with their robust nature, has made them invaluable tools in biotechnology and a subject of ongoing ethical debate.
Biological Identity of HEK293 Cells
A cell line is a population of cells derived from a single source that can be cultured for extended periods. HEK293 cells were originally derived from human embryonic kidney tissue, which provides the “HEK” portion of their name. Their stability, rapid growth rate, and adaptability to large-scale liquid suspension cultures make them highly desirable for industrial biomanufacturing. Despite their name, genetic and protein analyses have revealed that HEK293 cells exhibit characteristics of neuronal cells, rather than the epithelial cells typical of kidney tissue. This finding suggests the initial transformation may have targeted a less common neuronal lineage cell present in the original kidney culture. The cells are known for their complex karyotype, meaning they contain an abnormal number of chromosomes, specifically being hypotriploid with a modal chromosome number of 64.
The Creation and Origin Story
The HEK293 cell line was established in 1973 in Leiden, the Netherlands, by Frank Graham and his supervisor Alex van der Eb. Their goal was to create a stable human cell culture model for studying human adenoviruses. They began with primary human embryonic kidney cells and sought to alter them genetically.
The critical step was the introduction of sheared DNA from Adenovirus type 5 (Ad5) into the primary cells, a process known as transformation. A segment of the Ad5 genome, specifically the E1A and E1B genes, integrated itself into human chromosome 19. These viral genes produce proteins that disrupt the cell’s normal growth controls, granting the cell line its immortality. The “293” in the name refers to the 293rd experiment Frank Graham logged that successfully yielded the unique, immortalized cell clone.
Essential Applications in Research and Medicine
The presence of the adenoviral E1A/B genes allows HEK293 cells to function as highly efficient “mini-factories” in a laboratory setting. They are known for their high transfection efficiency, meaning they readily accept and express foreign DNA introduced by scientists. This makes them a preferred platform for producing large quantities of specific proteins, known as recombinant proteins.
They are widely used in the biopharmaceutical industry because they are human cells capable of performing human-like post-translational modifications (PTMs) on proteins. These modifications, such as glycosylation, are crucial for the stability and proper function of therapeutic proteins like monoclonal antibodies and recombinant clotting factors. This ensures the resulting drug candidates are more compatible and less likely to cause an immune reaction in human patients.
In gene therapy, HEK293 cells are considered the gold standard for packaging and manufacturing viral vectors, such as adeno-associated viruses (AAVs) and lentiviruses. Since the cells already express the Ad5 E1 genes, they provide the necessary helper functions to assemble and produce high titers of these therapeutic vectors.
The cells are also utilized in the development and manufacturing of various viral vector vaccines, including candidates for diseases like Ebola and COVID-19. They propagate the modified viral vectors that carry the genetic instructions for an antigen, stimulating the immune response. Beyond manufacturing, HEK293 cells serve as a model system for screening drug candidates, testing for toxicity, and studying the function of human receptors and ion channels.
Ethical and Public Perception Concerns
The primary public concern surrounding HEK293 cells stems from the source of the original tissue used to establish the cell line in the 1970s. The cells were derived from tissue obtained following a single elective termination of pregnancy. This origin has led to objections from various religious and pro-life organizations regarding the use of products derived from the cell line, including certain vaccines and biopharmaceuticals.
The cells used today are not the original fetal tissue, but rather highly replicated, modern descendants grown in laboratories for over fifty years. The controversy centers on the moral permissibility of utilizing a product that is distantly linked to an action that some view as unethical. This debate often involves a distinction between direct participation in an unethical act and the remote, historical use of a material that resulted from it.
While the scientific community emphasizes the life-saving nature of the medical advances made possible by the cell line, the ethical debate persists for certain consumers. Many organizations that object to the use of HEK293-derived products advocate for the development of alternative cell lines.