Our Future as Human Lobsters
On Sunday, scientists at the Harvard Dana-Farber Cancer Institute announced that they had succeeded in reversing age-related decline in mice, using genetic engineering techniques. The scientists created transgenic mice with a gene for telomerase expression that could be switched on and off with a chemical signal.
Telomerase is an enzyme which renews telomeres, repetitive regions of DNA that are attached to the ends of our chromosomes. Telomeres allow cellular replication to take place without loss of information; but after a certain number of cell divisions, the telomeres become depleted and no further replication can take place.
In mammals, telomerase is expressed by a gene which is only active in gametes, stem cells, very young somatic cells, and T-cells. T-cells, for example, distribute telomerase in younger humans, but stop doing so when we are around 45 years old. The absence of telomerase in older adult human bodies prevents new telomeres from being formed, which means that our stem cells are ultimately unable to continue to renew their own telomeres. Our stem cells begin to die as their telomeres are depleted, and we lose our capacity to regenerate tissue.
This process is a major component of the constellation of processes that constitutes 'ageing'. It contributes to the age-related loss of brain cells and cognitive function, loss of bone density, muscle wastage, wounds heal more slowly, and so forth. It has also been implicated in a number of age-related illnesses such as Alzheimer's disease, artherosclerosis, macular degeneration, and liver cirrhosis.
Human beings with abnormally low levels of telomerase suffer from premature aging. Lobsters, by contrast, express high levels of telomerase in their bodies throughout their lives, and their bodies remain characteristically youthful until they die. Because of these facts, it has long been hypothesized that we could age more like lobsters if we could simply increase the amount of telomerase in our bodies, leading to longer telomeres and longer cellular lifespan.
One major worry about this hypothesis has been that telomerase-based interventions would increase the rate of cancer. Cancerous cells switch on the telomerase gene in our DNA, allowing themselves to rapidly replicate and spread throughout the body. On the other hand, it is thought that the loss of telomeres is a major contributing factor to the formation of new cancers. Until now, we have had no indication of whether increasing telomerase would be beneficial or burdensome.
That is why this week's discovery by the Ronald DePinho's team at Harvard is exciting. They deactivated the telomerase gene in their transgenic mice, causing them to undergo premature aging in the form of cognitive decline and loss of fertility. Then they switch the gene back on, and the symptoms of age were reversed—their brains grew new tissue, their cognitive skills improved and their testicles began to grow and function normally. The treated mice lived longer than the mice whose telomerase gene remained inactive. Crucially, the mice did not show any significant increase in the rates of cancer.
As with any breakthrough in this field, we should not get too carried away too quickly. The mice did not live longer than normal, un-modified strains. There are major differences in mechanisms of senescence and cancer-resistance between mice and humans, so the beneficial effects may be smaller or absent in humans. And even in the best case scenario, telomere-shortening is only one component of age-related decline—we would still need to address other mechanisms which cause us to decline and die as we age, such as genetic diseases, cancers, glycation, and oxidation.
Finally, before we could implement a telomerase therapy in humans that could be used in a widespread way, we would need to find a way to do it that did not involve germline genetic enhancements such as those used in the experiments. A pill which increases our lives by a decade or more is still a long way off.
For all that, this result is one of the most dramatic leaps made in recent years toward the dream of radical lifespan-extending medicine. David Brin recently argued that there is no 'low-hanging fruit' in the development of lifespan-extending medicine, since human bodies already use most of the biological 'tricks' that can extend life in simpler organisms. On this view, every hypothetical treatment that could extend the lives of humans faces major practical obstacles which will delay their development by hundreds of years. Yet the Harvard discovery shows that one of the major obstacles to telomerase-based treatments—cancer—may not be an obstacle after all.
Life extension is nearing the border of science fiction and preparing to cross the border into science fact. These technologies will pose ethical challenges which our existing principles may be ill-equipped to deal with. For example, if we can treat the process of ageing, does this blur the line between health, disease and disability? If there are treatments that can reverse the effects of ageing, will we need to change how we we decide who deserves disability payments, what counts as discrimination, and how to deal with retirement?
Then there is the deeper problem of whether or not we should use these technologies at all. Most of the people I meet still say that they would refuse to use lifespan-extending medicines, even if those medicines conferred extended youth as well as extended life. Yet it is an axiom of medical ethics that we ought to save life when we can. Today, this axiom is relatively unproblematic to implement; once people grow old it soon becomes literally impossible to save their lives. Once we have radical life-extending therapies in hand, we will need to make a choice: either we choose to save life by extending it, or we choose to let people die once they have reached an 'appropriate' age.