a bit more on cell cultures, cell mortality and patients’ rights

Human connective tissue in culture, 500x. Image courtesy of Dr. Cecil Fox (photographer)/National Cancer Institute.
Canto: Well, we’ve followed up Meredith Wadman’s The vaccine race with Rebecca Skloot’s The immortal life of Henrietta Lacks, which intersects with Wadman’s book in describing cell cultures and their value in modern medicine and genetics. So are ready to talk about all this again?
Jacinta: Yes, this book tells a compelling history of the Lacks family as well as a story of the ethics around human cell cultures, based on the HeLa cell line taken from the cervix of Henrietta Lacks in 1951, shortly before she died of cervical cancer.
Canto: A very aggressive adenocarcinoma of the cervix, to be precise, though the tumour was misdiagnosed at the time.
Jacinta: Yes, her bodily state and her sufferings make for grim reading. And the cells were taken sans permission, in a pioneering era of almost no regulation and a great deal of dubious practice.
Canto: The wild west of cell and tissue culturology.
Jacinta: George Gey, the guy who ordered these cells to be taken, was a great pioneer in cancer and cell culture research, but he and others found it very difficult to keep human cells alive in vitro, so he was much surprised and delighted at his success with Henrietta’s tumour cells.
Canto: They were the first ever cells to live beyond the Hayflick limit, though that limit wasn’t spelt out by Hayflick until 1961.
Jacinta: And wasn’t accepted for decades after that. And the reason for their apparent immortality, a rare thing in untreated cells, was their cancerous nature. Human cancer cells contain an enzyme known as telomerase, which rebuilds the telomeres at the ends of chromosomes. Normally these telomeres, often described as like the protective caps at the ends of shoelaces, shorten and so become less protective with each cell division.
Canto: So if we could stop cancer cells from producing telomerase, you’d stop all that metastasising…
Jacinta: Sounds easy-peasy. And if we could introduce telomerase into non-cancerous cells we could all live forever.
Canto: Bet they haven’t thought of that one. So if this cell line was cancerous, how could they be of so much value? How could they be of any use at all, since the aim, I thought, was to produce ‘clean’ cells, like the WI-38 cells Hayflick produced ten years later? Remember how they had so many problems with monkey cells, which were full of viruses?
Jacinta: Well, forget viruses for the moment, the exciting thing about the HeLa cells was that they stayed alive and multiplied, which was rare, and so they could be experimented on in a variety of ways.
Canto: But did they use the cells for vaccines? The 1954 Salk polio vaccine was tested using these cells. How can you do this with cancerous cells?
Jacinta: Well it was the suitability of these cells for mass-production that made them ideal for test-driving the Salk vaccine, and of course their prolific nature was tied to their cancerous nature – Henrietta’s cancer seemed to be horribly fast-spreading, it was just about everywhere inside her at her death. Her cancer was caused by the human papilloma virus (HPV) and I’ve read that this may have had something to do with their prolific nature. She also had syphillis, likely contracted from her philandering husband, and this suppresses the immune system, allowing the cancer cells to multiply more rapidly. But even though they were cancer cells they shared many of the properties of normal cells, including the production of proteins and susceptibility to bacterial and especially viral infections. Of course you would never inject HeLa cells into humans, but their malignancy is an advantage in that you get the results of say, viral infection of cells as they reproduce, much more quickly than with normal cells, because of their reproductive rate. It seems old George Gey hit the jackpot with them, though he never made any more money out of them than the Lackses did.
Canto: They initially used rhesus monkey cells to test their antibody levels in response to Salk’s killed polio virus, but they were too hard to get and too expensive, and the HeLa cells were an excellent alternative because they were easily infected by the virus… and they reproduced with unprecedented alacrity.

The malignancy of immortality (or vice versa). A HeLa cell splitting into two new cells. The green spots are chromosomes. Courtesy Paul D. Andrews)
Jacinta: Yes, that’s to say, they readily produced antibodies, and so could be experimented on to produce the level of antibodies to create immunity. But growing cell cultures in vitro and maintaining them in a viable state, that’s been a decades-long learning process. Tissue culture these days is big business, which has led to the murky ethical questions about tissue ownership that Skloot refers to at the end of her book.
Canto: Yes but I for one am quite clear about that issue. I’m more than happy for researchers to use any tissue that comes from, say, a biopsy done on me. Is that tissue mine, when it’s removed from my body?
Jacinta: Well, is it? Think of locks of hair kept from a loved one – something that happens a few times in Skloot’s book. Wouldn’t you be moved by a lock of hair that you knew came from someone you loved but who was no longer around? Wouldn’t you feel you had hold of a part of her? Not just a memory of her?
Canto: Interesting. I think I’d be in two minds about it. I’d think, yes, this is her hair, a small part of her, and that would bring all the emotion of identity with it. But then, what I know about science and cells tells me this is just hair, it’s not what makes her her. It’s nowhere near it. Our hair is discarded all the time.
Jacinta: If you had some of her brain cells? Or heart tissue haha?
Canto: Nothing but ultra-ultra minuscule parts of the whole. And essentially meaningless when disconnected from that whole. But this misses the point that the value of this tissue for research outweighs by far, to me at any rate, the sentimental value that you’re talking about.
Jacinta: But for some people, and some cultures, the intactness of the human entity, after death say, is of deep-rooted significance. Are you not prepared to respect that?
Canto: But we slough off our trillions of cells all the time. Even as a kid I was told we replace our cells every seven years. Of course it’s much more varied and complicated than that, but the general point of constant renewal is true.
Jacinta: Yes but they’re your cells, with your DNA in them, nobody else’s.
Canto: Well people are prepared to be operated on, which inevitably kills or removes cells, and in doing so they give themselves up to experts in healing their bodies and often saving their lives, so it would seem to me pretty mean-spirited not to allow those experts to make use of what’s removed, which is of no obvious use to them.
Jacinta: I think you have a good argument there, but what if these mad scientists use your cells for some nefarious purpose?
Canto: Well, call me a trusting soul, but why would they do that? And what nefarious purpose could they use them for?
Jacinta: Well it mightn’t even be nefarious. With the modern commercialisation of cell and gene technology, they might find your tissue perfect for developing something patentable, out of which they make shitloads of money while preventing independent research on the tissue, so using your cells in a way that you might strongly disapprove of. But you wouldn’t have the slightest say, as things stand today. Rebecca Skloot describes examples of this kind in the Afterword to her book. There’s been a raging debate about commercialisation and gene patents and patients’ rights for some time now in the USA, and no doubt elsewhere, with scientists and other stakeholders ranged along the spectrum. In fact, these are the last words of Skloot’s book, published in 2010:
2009: More than 150,000 scientists join the American Civil Liberties Union and breast cancer patients in suing Myriad Genetics over its breast-cancer gene patents. The suit claims that the practice of gene patenting violates patent law and has inhibited scientific research.
Canto: Right. As her investigations reveal, it’s not just about patients wanting a share of the loot from research on their cells, and so using the courts to bog everything down and hinder that research, it’s often about researchers themselves wanting to cash in, and patients joining with other researchers to try to free up the system for the common good. So how’s the Myriad Genetics case going, and how’s the situation regarding patient rights in this field, several years on?References
Jacinta: Well in the case of Myriad, it was all highly complex and litigious, with suits and countersuits, which the company mostly lost, in particular in a landmark (and unanimous) Supreme Court decision of 2013, in which they found that ‘merely isolating genes that are found in nature [in this case the BRCA-1 and BRCA-2 genes] does not make them patentable’. But of course this wasn’t so much about patients’ rights in the material that was once part of their bodies. It’s not all about money – though much of it is, and if you don’t want the money landing in lawyers’ pockets, the best thing is to have clear guidelines, disclosure, and fully developed and complex consent procedures. My impression from doing a fairly shallow dive on the issues is that we’re a long way from sorting this out, in an increasingly complex and lucrative field. Our own federal government’s NHMRC has a booklet out, available on PDF, called ‘Ethics and the exchange and commercialisation of products derived from human tissue: background and issues’, which is already six years old, but I don’t see anything in the legislative pipeline.
Canto: Looks like an issue to be followed up, if we have the stomach for it.
Jacinta: It pays to be informed, that’s one obvious take-away from all this.
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