Definition, Importance, Medical Breakthroughs, Microscopy
Definition: What are HeLa Cells?
HeLa cells refer to a line of cells belonging to a strain that has been continuously cultured since 1951. Compared to other human cells, HeLa cells were (and still are) the only cells to survive in vitro. As such, they are often regarded as the first (and thus far, only) immortal human cells ever cultured.
Brief History of the HeLa Cell
In 1951, a 31-year-old African-American woman by the name of Henrietta Lacks was brought to John Hopkins Hospital in Baltimore regarding a lump in her abdomen. The diagnosis revealed that Lacks was suffering from an aggressive type of cancer (adenocarcinoma of the cervix or adenoepidermoid tumor) which doctors tried to treat using radiation-tube inserts (Brachytherapy). During her treatment, her doctor also removed a piece of her cancer tumor for culture studies without her knowledge or consent.
For years, the surgeon had been collecting tissue samples from other patients for cancer research studies (led by the then Director of the Tissue Culture Laboratory at John Hopkins, Dr. George Gey) with the aim of finding a cure for cancer. Although many other cancer tissues had been cultivated, they failed within a few generations.
In vitro cultivation of Lacks' tissue, however, proved successful with millions of her cells, known as HeLa cells, still alive today.
* The name HeLa (for HeLa cells) was derived from the first two letters of Lacks' first and last names.
* The identity of Henrietta Lacks was revealed in the 1970s.
HeLa Cells Contamination Issues and Significance
In 1967, works of Stanley Gartler, Ph.D. found that HeLa Cells had contaminated other human cell lines. This, as well as additional findings involving contamination, was an important discovery that influenced the reappraisal of tissue culture stocks by the ATCC (American Type Culture Collection) and the Cell Culture Laboratory at the Naval Biosciences Laboratory.
The HeLa cell contamination had therefore brought to light an important culture contamination issue for the scientific community as a whole. For instance, according to one of the studies, cancer cell lines from human breast tissue were found to have intra and interspecies contamination.
From this and other studies, it became evident that a concerning percentage of all cell lines were not what they were deemed to be. Apart from issues of contamination, this discovery was also important in that it highlighted another important issue; that of misattributing given property to a given cell line.
Through contamination of given cell lines by another, certain attributes of the contaminant could be misattributed to the cell line under investigation thus affecting the results of the study. In scientific research, this was a real issue that had to be addressed. This discovery, therefore, was an important one in that it raised awareness and a need for better handling of biological samples (cells, tissues, etc) to avoid contamination.
* HeLa cells have been referred to as laboratory weed in some spheres because of their persistent contamination of other cell lines.
Three Major Characteristics
Compared to other human cells that researchers have attempted to culture and cultivate, HeLa cells have the following unique characteristics:
Obtained from cancerous tissue, HeLa cells are also cancerous cells and thus have different genetic characteristics as compared to normal human cells.
Following genetic studies on the cell, it was observed that like many other tumor cells, the HeLa cell contained many errors in its genome. Compared to the normal cell with 46 chromosomes, chromosome copies of the cell (HeLa) was shown to contain between 76 and 80 chromosomes with a good number of these being highly mutated.
According to recent studies, HeLa cells were shown to contain DNA of the HPV virus (Human Papillomavirus). HPV is a major cause of cervical cancer that acts by inserting its DNA into the cells of the host. The resulting DNA produces a protein (p53-binding protein) that prevents p53 from mutation repair and tumor suppression. In HeLa cells, this was shown to contribute to changes in microRNA expression and ultimately to the prolific growth of the cells in culture.
High Growth Rate
Compared to normal cells, HeLa cells were shown to grow unusually fast even with their cancerous state taken into consideration. In addition, they have proven easy to grow which in addition to their rapid growth (double in a 24 hour period), has made them ideal for large scale research studies.
Because of their ability to multiply rapidly, HeLa cells are also capable of easily contaminating and outgrowing other cell lines in culture.
* The unusual fast growth of HeLa cells has been attributed to the fact that Lacks had syphilis and HPV. The presence of HPV genome, as well as syphilis, suppresses the immune system in such cases thus allowing for the proliferation of the cells.
As "immortal cells" the HeLa cells divide repeatedly which has allowed researchers to cultivate them for the past 6 decades. This aspect of the cells has been attributed to the expression of overactive telomerase allowing for the rebuilding of telomeres in each division. As a result, this has prevented cellular senescence which in turn has allowed cell division to continue for so long.
Importance and Disadvantage of HeLa Cells
Compared to normal human cells, HeLa cells have a number of unique traits (discussed above) that make them very important for medical and biological studies.
Because they are immortal, experiments can be conducted on identical cells (clones of the original HeLa cells). This is a significant advantage that normal, healthy human cells lack.
While HeLa cells have several advantages that have made them extremely useful in medical and biological studies, they also present a number of disadvantages.
Apart from the fact that they can aggressively contaminate other cell lines, thus affecting research study results, HeLa cells do not have the normal human karyotype.
As previously mentioned, the genome of these cells can contain as many as 80 chromosomes with the extra chromosomes being the result of infection. As a result, there are limitations as to the extent to which the cells can be used.
Regardless, the HeLa cells have been successfully used and been at the center of several medical breakthroughs over the past 6 decades.
Uses and Medical Breakthroughs
Because of their unique characteristics, HeLa cells have been used in a number of experiments that have involved testing the impact of toxins, cosmetics, radiation and various types of chemicals on human cells which has made them valuable in a number of industries.
The following are some of the other experiments in which the cells have been used over the years:
Study the Impact of Zero Gravity on Human Cells
In 1960, HeLa cells were sent to space with the Soviet satellite, Korabl-Sputnik. Later, NASA also placed the cells in the Discoverer XVIII satellite on a mission to space.
The main aim of this was to determine the impact that zero gravity would have on human cells. From the experiment, it was discovered that the cell divided even faster in zero gravity. Therefore, HeLa cells, along with the cells or other organisms, have played an important role in learning about space biology.
Gene mapping refers to techniques through which researchers identify given locus and distance between genes. Through gene mapping, then, researchers are able to identify and even place markers on given positions of the genome they wish to study.
In 1965, HeLa cells were fused with mouse cells in a study that was conducted by scientists John Watkins and Henry Harris. In the process, the two created the first human-animal hybrid cell which in turn set the stage for gene mapping.
Through this experiment, scientists could observe the impact of different genes added to the DNA. For instance, in the case of the HeLa cells, it was possible to observe the type of proteins that were produced by the human gene (from HeLa cell) in the animal. Therefore, the HeLa cell can be said to have helped set the stage for mapping of the human genome.
In 1984, the original sample of Lacks' biopsy was tested by Harald zur Hausen, a virologist. The sample revealed the presence of human papillomavirus, which in turn allowed him to identify the virus as the cause of cervical cancer.
From the study, the researcher found out that by forcing its DNA into normal human cells, the virus took control of the cell forcing them to produce various proteins associated with cancer. This proved to be one of the most important discoveries in that it allowed other scientists to use the knowledge to develop vaccines against the virus.
Today, HPV vaccines are available in virtually every country and help protect young girls from the risk of HPV infections. According to statistics, the vaccine has helped reduce HPV by about two thirds and prevents deaths associated related to cervical cancer by about 70 percent.
Eradication of Polio
Apart from HPV vaccination, HeLa cells played a significant role in polio eradication. In the 1950s, polio was one of the most serious viral diseases that affected many people.
Although a vaccine had already been discovered by Jonas Salk, a medical researcher, and virologist, testing it presented a problem given that using rhesus monkeys would be extremely expensive (large scale testing). Since HeLa cells were discovered at approximately the same period of time, they proved ideal for the test as they were susceptible to infection, but could not be killed by the virus (the polio virus).
The ability of HeLa cells to rapidly multiply in particular proved ideal for the test given that it allowed for continued testing. Using these cells, Salk was able to test the vaccine on a large scale and determine its effectiveness.
With the test proving successful, it was concluded that the vaccine was safe to use. Today, the polio vaccine continues to be used all over the globe with excellent results.
* According to statistics, polio is about to be completely eradicated globally.
Some of the other areas in which HeLa cells made significant medical and scientific contributions include:
· Chromosome counting - In 1953, a small laboratory mix-up resulted in the cells (HeLa cells) being mixed with a liquid that caused chromosomes of the cell DNA to unwind. As a result of this small accident, researchers were able to clearly observe and count the number of chromosomes of the cell. This allowed for the development of a staining technique that made it possible to effectively count the number of chromosomes in human cells.
· Virology - Using HeLa cells as test subjects, different types of viruses have been tested to determine their action on human cells.
· Improved laboratory practices - As already mentioned, contamination of other cell lines with HeLa cells resulted in a need for better laboratory standards internationally.
· Extended cell lifespan - By observing the HeLa cells, researchers have been able to understand how some cells remain young over time.
* Although the HeLa cell and research studies on the cells have allowed for many discoveries that have benefited humankind, it also raised an important issue regarding consent and privacy. This is largely due to the fact that Lacks did not give consent for her cells to be used for research studies at such a wide capacity. In addition, it raised questions regarding the patient's privacy and confidentiality: Protecting the privacy of the patient and their medical information.
A number of Nobel prizes have been awarded to several scientists for contributions in their fields through their work with the HeLa cells.
· Elizabeth Blackburn, Carol Greider, and Jack Szostak - awarded the Nobel prize in 2009 for their work that resulted in the discovery of the cellular clock
· Zur Hausen - Awarded the Nobel prize for his work that resulted in the development of HPV virus
· Richard Axel - Awarded the Nobel prize for his work on the HIV virus and the HeLa virus
· Jonas Salk - Awarded the Nobel prize for his work that led to the development of the polio vaccine
To observe the HeLa cell and some of the internal components (mitochondria) under the light microscope, the following procedure may be used:
- Wash cultured cells with Eagle's medium
- Fix the cells in formaldehyde for about 10 minutes (at about 4 degrees Celsius)
- Wash the cells about 3 times using 0.44M sucrose in cacodylate buffer
- Expose the cells to the DAB incubation medium for about 3 hours
- Wash the cells twice at room temperature using sucrose in Tris buffer
- Treat the cells with osmium tetroxide for about one hour
* Using this method, the cells may be observed under the light or electron microscope.
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Brendan P. Lucey, MD; Walter A. Nelson-Rees, PhD; Grover M. Hutchins, MD. (2009). Henrietta Lacks, HeLa Cells, and Cell Culture Contamination. Historical Perspectives.
J. W. Posakony. J. M. England and G. Attardi. (1975). Morphological Heterogeneity Of Hela Cell Mitochondria Visualized By A Modified Diaminobenzidine Staining Technique. J. Cell Sci.
Nancy L Delaney and Roger Kennett. (1976). Genetic characteristics of HeLa cells. ResearchGate.
The Copia Institute. (2015). HeLa Cells: Grown Without Permission, For The Benefit Of Medicine. The Legacy Of Henrietta Lacks Lives On.