Adventures in Immortality
In the winter of 1951, a thirty-one-year-old woman named Henrietta Lacks was admitted to Johns Hopkins Hospital in Baltimore, Maryland. Lacks was complaining of feeling a ‘knot’ on her cervix and believed she might be pregnant again. But instead, doctors found a visible lesion. She had cancer. Through 1951, the cancer metastasised and spread all over Lacks’ body, ultimately killing her later that year.
Before the death of Henrietta Lacks, doctors had studied cells from her cervical biopsy in culture in the laboratory. Normally, this is hard. Human cells are not fond of growing in culture and tend to die quickly outside the body. But the cancer cells of Henrietta Lacks seemed to thrive just fine.
Doctors were baffled as they watched the cells dutifully divide, day after day.
When Henrietta Lacks passed away, her cell sample was still very much alive in the laboratory. And this is where the story gets murky. As the cells of Henrietta Lacks were the first culturable human cell line that was a big deal scientifically. The scientists involved started eagerly sharing the cells with other scientists, but they never consulted Henrietta Lacks or her family. I will let you be the judge of the morals here; Johns Hopkins issued an apology over 50 years later.
The point is that the cells of Henrietta Lacks live on to this day. The cell line, called HeLa, is immortal, and the free sharing of cells means that it is used all over the world today. Just a few years after the death of Henrietta Lacks, it was used by Jonas Salk to develop the first vaccine against polio. And since then, HeLa cells have been used millions of times in cancer research, virology and basic biomedical science.
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At the end of a shoelace, there’s a piece of plastic or metal that ensures the lace doesn’t fray. I bet you never wondered what those things are called. They’re aglets. That might sound like a completely irrelevant fact in a book about ageing research, but your cells actually face a similar problem to that dealt with by shoelace manufacturers. You see, inside your cells, your DNA is contained in long thread-like structures called chromosomes. And the ends of these chromosomes can get damaged or frayed, just liked the tips of shoelaces. Your cells solve the problem with something called telomeres, which are like genetic shoelace aglets. Telomeres are made from the same building blocks as the rest of your DNA – nucleotides – but the difference is that telomeres don’t contain any important information. They have no genes, and are just made up of the same sequence repeated again and again. That’s clever, because it means our cells can lose some telomere and be alright. At least in the short term. In the long term, our telomeres are actually a cornerstone in determining the lifespan of our cells.
We once thought cells were immortal, even though organisms as a whole age and die. But then a scientist named Leonard Hayflick proved that normal human cells will die after they have divided a set number of times. This phenomenon is now called ‘Hayflick’s limit’ and it is caused by our telomeres. When we’re born, our telomeres consist of approximately 11,000 nucleotides. But every time our cells divide, the telomeres get a little bit shorter. That’s fine, until they become so short that our useful DNA becomes jeopardised. Before this can happen, the cell pulls the emergency brake and stops dividing.
In this way, the shortening of telomeres is what makes cells mortal. Even if we somehow enabled cells to continue dividing after they reach Hayflick’s limit, cells would eventually lose the telomeres entirely. That would expose DNA to damage and the cell would die anyway.
However, maybe you can think of at least one possible solution. What if we just elongated the telomeres to cancel out the loss? That’s actually what some cells do. We have an enzyme called telomerase, which is what makes our telomeres in the first place. You can think of telomerase as a little molecular machine that goes to the end of chromosomes and elongates the telomeres. Cells mostly use telomerase during development when we grow from a single cell to billions in a short time. That requires a lot of cellular divisions, and telomerase makes sure we don’t run out of telomeres before life even gets started. Soon after development is finished, though, the vast majority of our cells turn off the telomerase gene and become mortal.
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Telomerase is the reason the cancer cells of Henrietta Lacks became immortal. Lacks’ cancer was caused by the virus
HPV-18 (Human Papillomavirus 18), which causes the majority of cervical cancers in the world. In the process of infecting Lacks, the virus turned on the gene that makes telomerase. That means the virus gave the cells an ability to continuously elongate their telomeres and thus divide again and again
without ever running out. That’s pretty helpful for a cancer, and it’s also what keeps the HeLa cells immortal to this day. If scientists block the telomerase enzyme in the HeLa cells, they lose their immortality and die after a set number of divisions, just like their pre-cancerous ancestors.
Think about that for a moment. We actually know how to make cells immortal. And you and I consist of lots of cells – 37 trillion, to be exact. However, is making cells immortal the same as making the organism immortal? If it is, the way to prolong life is to keep our telomeres from becoming short. Researchers have investigated this approach by breeding mice that are born with abnormally long telomeres. Not only are these mice leaner than normal mice, they also have healthier metabolisms, age better – and, ultimately, live longer.
We also have suggestive evidence from humans. People born with mutations that cause rapid shortening of the telomeres age prematurely. And even within the normal variation, telomeres are associated with ageing. As with all other traits, there are differences in telomere-related characteristics between individuals. Some people have longer telomeres than others, and some people lose telomeres more slowly throughout life. In a Danish study of 65,000 people, those with shorter telomeres had a higher mortality rate and a higher rate of age-related diseases, such as cardiovascular diseases and Alzheimer’s.
So, should we try to elongate our telomeres? Scientists haven’t tried this officially – but someone outside the normal bounds of academia has.
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In 2015, an American woman travelled to Colombia hoping to launch a life-extension revolution. Liz Parrish, as she is called, is neither a mad scientist nor a rich weirdo. In many ways, she is your average suburban mum.
While working on stem cell advocacy, Parrish learned about the powers of telomerase. Scientists showed her how mice with long telomeres will be bouncing around full of youthful energy while similarly aged normal mice will sit in the corner, old and frail.
Parrish dreamed of transferring this magic to humans, but learned that it would be hard. Scientists have tried making drugs that turn on the telomerase enzyme, but it has proven very difficult. Instead, Parrish opted to use something called gene therapy. This is a newer medical invention where scientists add an extra gene to a person’s cells, a bit like adding a spare part. In this case, the genetic spare part would be an extra (and active) telomerase gene.
Liz Parrish didn’t travel to Colombia because Colombians especially need to have their telomeres elongated. Instead, she left her home country to get away from the Food and Drug Administration. Parrish wanted to use herself as the first test person, but the United States, and most other developed countries, severely restricts the type of medical procedures you’re allowed to carry out – even if it’s just to your own body. Injecting a gene therapy you came up with yourself would never fly.
And so, Parrish flew instead. In Colombia, she found a clinic that was willing to help her out. First, scientific collaborators measured Parrish’s telomeres so that the efficacy of the treatment could be determined. They found that she actually had significantly shorter telomeres than expected for a woman her age. Not the worst test person.
Then, Parrish received her gene therapy injections and, after a bit of monitoring for acute side effects, she went back to her home country. The following year, it was time for the results, and once again, Parrish’s scientific collaborators measured the length of her telomeres. The results were positive. It seems Liz Parrish is the first person ever to successfully elongate her telomeres.
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Liz Parrish’s self-experiment caused an uproar in the scientific community. On one side, proponents argued that the self-experiment would provide valuable data for the rest of us. On the other side, critics considered the whole ordeal dangerous – reckless, even – and feared social contagion. Parrish herself has defended her position and has been quoted as saying: ‘To get US government approval to bring gene therapies to you . . . I would have to go raise almost a billion dollars. It would take about fifteen years of testing. And when I’m looking out there, I’m seeing people who don’t want to wait fifteen years.’
However, let’s take a step back. It’s true that we could argue about whether or not a self-experiment like this is safe. But the most important question is whether it would be worthwhile even if it worked. Think about it: I told you all our cells have the gene for telomerase. But early in life, they turn it off and keep it like that. If the secret to a long life is telomerase, why wouldn’t our cells just turn the enzyme back on and use it?
The reason turns out to be an ugly trade-off. Maybe you can guess it from the story of Henrietta Lacks. It is true that telomerase can make cells immortal. But that’s exactly what the cells of Henrietta Lacks became – and how did that turn out for her? The problem is that the telomerase gene is essential in the development of cancer. Eighty to ninety per cent of all human cancers find some kind of way to turn on the telomerase gene. Even the ones that don’t do this usually find another way to elongate their telomeres. They have to. Without continuous elongation of the telomeres, the cancer cells would eventually die, just like normal cells.
To be fair, advocates for telomere extension, such as Parrish, don’t favour immortalising one’s cells. They hope to turn on telomerase briefly – just enough to slightly elongate the telomeres, but not enough to make cells cancerous. It’s not actually clear whether those things can be separated, though. Studies show that people who have longer-than-average telomeres are at a higher risk of getting cancer. So it seems that messing with telomeres is a dangerous project at best. As our ability to fight cancer keeps improving, it might someday become worth it to take the bet. But until then, I’d stay away. Nature has probably already considered the ageing/cancer trade-off and set telomere length accordingly.
Besides, there are also other problems with telomere research: mainly that most studies use mice as their model organism. Mice are often a good way to model humans, taking cost and difficulty into account, but they’re not a good model organism when it comes to telomeres. Telomere biology in mice is very different than it is in us; mice have active telomerase in all their cells and are also born with much longer telomeres than we are. If telomeres were the only source of youth, mice would live substantially longer than us. But they don’t – mice struggle to live even a few years while succumbing to cancer at high rates. On to the next one.
In 2016, American astronaut Scott Kelly came back from what was then the longest stay for an American aboard the International Space Station. Back on Earth, he was met by his loved ones, including his identical twin brother, Mark Kelly, who is also an astronaut. NASA examined both twins before, during and after the journey to learn about the physical effects of long stays in space. They found that spacefaring Scott underwent many physiological changes that earthbound Mark didn’t. One of them was that Scott’s telomeres got longer while he was in space. But once he was back on Earth, they quickly shortened again, and actually ended up shorter than they were before the trip.
Maybe the Fountain of Youth is a one-way ticket to space . . .