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HeLa Cell line: Immortal legacy in biomedical research

Henrietta Lack’s memory and name lives on in the form of continually dividing immortal cell linesHeLa that continues to divide and grow today and is a key human cell line resource to understand the causes and treatment of human cancers.

DR SANJUKTA DAS |

Anyone associated with biological research knows HeLa cell lines are the first recognized human immortal ‘cell line’ to be established in culture and most extensively used in biological research.

Immortalised cell lines refer to the cells that have been transformed in a way to be cultured indefinitely and therefore offer many advantages in scientific research as they are well characterised and easy to culture so also do not require extraction from an animal. They also constitute a homogeneous group of cells being genetically identical, providing reproducible and consistent results in the experiments that utilise them.

Immortalised cell lines are derived from a variety of sources that have mutations that make them alive for many generations. Brief story line of HeLa cells One famous and well known cell lines is the HeLa cell lines which have been named after the patient’s name Henrietta Lacks. It is not so common to provide an eponym in the patient’s name. In the medical lexicon few eponyms are there honouring patients.

However, immortal HeLa cell lines are named after the patient who was the donor who has a lasting contribution to biomedical research. Immortal cell line is nicknamed as a coded language after its ancestor – He for the first two letters Henrietta and La for the first two of Lacks. The power of Lack’s cell lines is its immortality, that is it can be grown indefinitely.

The best-selling book “The Immortal Life of Henrietta Lacks”, written by Science writer Rebecca Skloot throws light on the story of HeLa cells and their ancestor Henrietta and brings them closer to public knowledge. HeLa cells originated in 1951 from Cervical tumor of Henreitta Lacks, a 31-year-old African-American woman, who went to Baltimore’s John Hopkins hospital to get treatment for cervical cancer. Her surgeon Dr George Gey, director of the tissue culture laboratory at John Hopskins took the tissue sample of his cervical cancer with an objective to create immortal cell lines for cancer treatment. However Dr Gey was not successful in his past attempts of tissue culture, but he was successful with tissue retrieved from Henrietta’s tumor.

As Skloot describes, Dr Gey’s culture media was a cocktail having liquid with extracts from heart of chicken, calf embryo and blood from a human umbilical cord and this nutritional media could sustain Henrietta’s cancer cells which continued to multiply at an unprecedented rate and this led to the emergence of first immortal human cell line in the name of HeLa cell line.

Since then and after Lack’s demise in 1952, the cervical cells derived from her have come important tool in many biomedical research labs. Characteristics of HeLa cell First and foremost that characterizes HeLa cells is their immortality in culture that is having endless division when grown in appropriate nutrient medium. It is a cell line representing the first breakthrough in immortalising human derived cells in laboratory conditions.

The HeLa cells karyotype reveals chromosomal aberrations and mutation in their genome. These cells contain 76-82 number of chromosomes instead of the normal 46 number of chromosomes and some of the chromosomes have mutational errors of deletion, duplication and translocations.

The HeLa cell genome exhibits high levels of aneuploidy due to the presence of an extra number of chromosomes which has resulted from the infection of HPV (Human Papilloma virus) leading to carcinoma. As a result the HeLa cells are transformed and grow easily and rapidly in-vitro conditions. When cultured, they double in number in 24 hours making them an ideal robust research model for various experimental works.

Normal human cells in culture pose limitations to researchers in terms of repeating their experiments on clones of cells as normal cells reach Hayflick limit after a specific number of divisions and then they cease dividing and die due to senescence.

This occurs as a result of gradual shortening of telomeres that are repetitive DNA sequences at the end of the chromosomes protecting them from being tangled or frayed. Due to limited cell divisions, experiments cannot be performed for a longer period of time or can be repeated a number of times. On the other hand HeLa cells provide researchers an opportunity of constant supply of cell lines to work on as they have ability of infinite cell division overcoming Hayflick’s limit as they maintain telomerase enzyme that prevents shortening of telomeres (hexanucleotides) of chromosomes.

The transcriptome of HeLa cells have been profiled with the help of second-generation sequencing technologies (Affymetrix ENCODE transcriptome project and Cold Spring Harbor Laboratory ENCODE Transcriptome Project 2009). Research analysis has shown that genes for proliferation, transcription and specific DNA repair mechanisms are more active and enriched in HeLa cells as compared to normal human cells.

Scientific breakthroughs achieved by use of HeLa cells NIH (National Institute of Health) has made an elaborate analysis and evaluation of scientific achievements made on the use of HeLa cells and found 110,000 publications that mentioned the use of HeLa cells between 1953 and 2018.

Many breakthroughs have been achieved in biomedical research on using this cell-line. In 1954, Jonas Salk used them to develop the polio vaccine. In 1966 HeLa cells were utilised to understand RNA metabolism in the nucleus. In 1979 it was demonstrated via HeLa cells that glutamine is a necessary energy source for cancer cells rather than sugar. In the 1980s the use of HeLa cells by AIDS researchers helped them to isolate and identify HIV virus.

Two Nobel prizes have been awarded for discoveries where HeLa cells played crucial role – in 2002 by Dr Harald Zur Hausen for showing that viruses can cause certain cancers and in 2009 Dr Elizabeth Blackburn, Dr Carol Greider and Dr Jack Szostak for telomerase enzyme impacting telomere length. These cells have helped scientists in developing drugs for leukemia, influenza, haemophilia and Parkinson’s disease.

They are also used in the study of lactose digestion, sexually transmitted diseases, appendicitis, human longevity etc. Besides, HeLa cells also had gone a long way in contributing to the “Omics” revolution from genomics to transcriptomics and proteomics. Henrietta’s cells have gone on space missions to learn the effect of zero gravity on cells.

Even other scientific landmarks such as gene cloning, gene mapping and in vitro fertilization have been carried out utilising HeLa cells. HeLa cells use has helped researchers to understand the nuances underpinning diseases from bacterial infections to cancer. Most recently this cell line is also used to study the effect of SARS-CoV replication in the human body. Because of frequent contamination of HeLa cells with other cell lines they have often been referred to as “laboratory weeds”. HeLa cell contamination with other human cell lines raised an important issue in scientific research that is the need for better handling of biological samples such as cells and tissues to protect them from contamination.

There is another angle to HeLa cell line story that is the issue of informed consent in health care. In 2013, NIH director Francis Collins in an article in Nature had stated that Henrietta Lacks posthumously continues to make contributions to science, not only in regards to scientific impact of the HeLa cell line, but also by promoting modern policy and ethical considerations that prioritize human subjects protection, privacy and respect.

Henrietta Lack’s memory and name lives on in the form of continually dividing immortal cell linesHeLa that continues to divide and grow today and is a key human cell line resource to understand the causes and treatment of human cancers.