How does one accidentally evolve a population of cells? Quite easily it seems.
This story begins in 1951, when Henrietta Lacks went to see her doctor at Johns Hopkins Hospital. She had cervical cancer. A biopsy of her tumor was taken, which then fell into the hands of a scientist by the name of George Gey, who was working on trying to culture the first human cells in the lab. Henrietta’s cells, to Gey’s surprise, flourished in the rich environment he had created for them, quickly growing far beyond their original volume. With letters taken from the first and last name of Henrietta Lacks, he called them HeLa.
Meanwhile, as Henrietta’s cancer proceeded, the aggressiveness of the tumor caused it to spread throughout her body, and eventually resulted in her death just a few months later. The cells taken from Henrietta’s tumor grew and grew and grew, now surpassing the weight of the body they were once a part of. They were immortal. HeLa had found a way to cheat death, and divide indefinitely.
The limit to cellular replication is the length of the ends of the chromosomes, termed the telomeres, and through each replication cycle, a small part of the DNA is lost. After many years of replication of chromosomal DNA, the telomeres reach a critically short length and cells essentially give up (senescence). However, the HeLa cells did not give up. Through the random mutations accumulated in cancer, the cells managed to activate a part of the cellular machinery to lengthen the telomeres, an enzyme called telomerase .
Since these cancerous cells had the ability to essentially live forever and survive in a lab, HeLa cells became the perfect tool for medical research. Following their discovery and use by George Gey, over 60,000 papers have been published using HeLa, which of course led to the identification of telomerase in chromosome maintenance, the development of the first polio vaccine, and many more life saving discoveries. However, given the very nature of cancer cells, they can undergo rapid changes through mutations, allowing them to evolve over a very short time period (as what happens in human bodies when cancer progresses).
Therefore, some people began to wonder, are HeLa cells evolving? If they are, what effect does this have on recently made medical discoveries using these cells? Are they even human anymore?
With these questions in mind, an Italian group of researchers sought to find the answers.
There is a standard practice when it comes to culturing HeLa cells. A medium was manufactured for their specific growth needs, and virtually all tissue culture labs around the world use these same products. That is what makes the culturing of human cells so relevant in the field of experimental evolution, whether it is on purpose or not.
These researchers knew of other groups in the field that had been culturing the same HeLa cells for 8 and 12 years continuously, potentially accumulating multitudes of differing mutations. Therefore they sought to find out exactly how distinct these cell lines were from the original human genome (since Henrietta never had any normal tissue taken for us to sequence).
To get a general idea for the amount of divergence between the HeLa cell lines and also the normal human genome, the researchers carried out simple karyotyping, basically visualizing and counting chromosomes under the microscope. Now, just to get an idea of a normal set of chromosomes, you need to know that humans usually have a total of 46 chromosomes (23 pairs). The HeLa cells are clearly not “normal”.
Cells that had been continuously cultured for 8 years had chromosome numbers ranging from 71 to 79. Almost double that of a typical human.
And even more shocking, the cells that had been continuously cultured for 12 years had chromosome numbers ranging from 56 all the way to 240!
To further demonstrate the evolution of these HeLa cells from known common HeLa markers, the researchers used Fluorescent In Situ Hybridisation (FISH for short) to “paint” certain chromosomes different colours.
The image above shows chromosomes that contain the DNA of chromosome 5 and chromosome 9, with a myriad of each present.
Just FYI, humans usually have two copies of each chromosome (with my very own chromosomes for reference!).
Clearly, these cells may be a little inaccurate when being used for medical research if some have far more chromosomes than they should.
Now knowing that there were definitely huge differences in chromosome number, the researchers then wanted to know which specific parts of the genome were actually being gained or duplicated. So they showed the sequenced genomes of 2 groups of HeLa cells grown for 8 years (HeLa P and HeLa H derived from the same batch) or 12 years (HeLa V and HeLa SR derived from the same batch) continuously, compared with the human genome.
The above Circos plot above showed that each HeLa line had a huge proportion of genetic information deleted (in red) or duplicated (in green) from the human genome, but with lines derived from the same batch somewhat similar. This picture illustrates just how different a cancer genome is from normal human cells, and also shows the differing evolution of cancer cell lines grown under very similar conditions over time.
It is obvious, at least to me, that these cells are vastly different from humans. It has actually been proposed that HeLa should be classified as a new species, Helacyton gartleri, but unfortuantely the name just never caught on.
Most scientists that culture cancer cell lines know that the nature of these cells allows for them to accumulate mutations, and eventually become unreliable in terms of testing for real-world medical applications. Therefore, it is standard practice to not continually culture your cells for more than a couple of months (about 50 transfers to new media). But clearly, this message has not reached everyone in the field, and this is a cautionary tale to all those who do not heed the information gathered in this paper.
All of this information together tells us two things.
Firstly, that cancer cells grown in culture can evolve rapidly, analogous to the way in which a benign group of cells can undergo changes to become an aggressive cancer in the human body.
And finally, that you should never let your HeLa cells run rampant for 10 years.