Few people know more about how human life works than Cambridge’s Nobel prizewinning molecular biologist Venki Ramakrishnan. Now he’s pondering life’s most profound question.
The key to a long life is hardly a secret: eat and sleep well, get some exercise, avoid being hit by a bus and hope that any hereditary diseases skip your genes. Venki Ramakrishnan, a vegetarian who cycles to his Cambridge lab every day, does all these things and, at 71, says he is “philosophical” about his own death. But he also takes pills for blood pressure, high cholesterol and blood clots: magic medicines that extend our lives and are taken by millions of people each day.
If he were offered a pill at the end of his days, which rather than merely warding off disease actually circumvented the ageing process itself and granted another ten years of life, would he take it? “We would all be tempted,” Ramakrishnan says. “The will to live longer is deeply ingrained in each of us.” Could such a drug ever exist? “I have the sense that we’re on the cusp of something,” he says. How long could humans live? “I don’t think there’s any scientific law against breaking our natural barrier of 120 years or so. But I would put it in the same category as being able to colonise Mars. There’s no physical law saying we can’t do it. But it’s very difficult.”
Few people know more about life — and the cellular workings that drive it — than Ramakrishnan. The molecular biologist won the 2009 Nobel prize for chemistry for his work solving the structure of the ribosome, the part of the cell that reads genetic instructions and uses that information to make proteins. The ribosome is crucial to how our bodies work: it dictates the colour of our eyes, ensures our hearts beat and minds whirr. It was an astonishing breakthrough.
Ramakrishnan was knighted in 2012, elected president of the Royal Society in 2015 and in Queen Elizabeth II’s final honours list he was appointed to the Order of Merit, of which there are only 24 members, among them David Attenborough, the artist David Hockney and the architect Lord Foster of Thames Bank. Now, having made such a success of unearthing the secrets of life, Ramakrishnan is focusing his microscopic gaze on what causes that life to end. He has written a book called Why We Die.
The Egyptians built the Pyramids to prepare their pharaohs for the afterlife; Chinese emperors were entombed with terracotta armies to defend their bodies until rebirth. Hindu reincarnation and karma, Christian heaven and hell, Islam’s garden of everlasting peace: these doctrines arose because, as Ramakrishnan puts it, “the knowledge of death is so terrifying that we live most of our lives in denial of it”. The title of his book alone is enough to bring many of us out in a hot panic.
However, as religion’s grip weakens, a void has been left in our relationship with death. Instead of priests and prophets, we are increasingly turning to a group of people — many of them ultra-wealthy men — whom Ramakrishnan calls “immortality merchants”.
Ramakrishnan was brought up in Vadodara in Gujarat in a Hindu family, though with two scientists for parents — his father was a biochemist, his mother an experimental psychologist — he had a relatively secular upbringing. “But as the joke goes,” he says, “in foxholes and exam halls, nobody’s an atheist.”
I meet him at the Medical Research Council’s Laboratory of Molecular Biology in Cambridge, where he has worked for 25 years. This soaring institution on the Addenbrooke’s Hospital campus is the source of 12 Nobel prizes, including Francis Crick and Jim Watson’s 1962 award for discovering the structure of DNA. The lab and its 440 scientists aim to “tackle major problems in human health and disease”. But outside the world of academic science, researchers are no longer content simply to fight disease — they want to cheat death itself.
Just 10km from where we are sitting is Altos Labs, the most heavily funded biotech start-up ever, with £2.4 billion ($5 billion) from investors including Amazon’s Jeff Bezos and the Israeli-Russian billionaire Yuri Milner. Opening in Cambridgeshire in 2022, the facility has the goal of halting the ageing process altogether. In the past decade more than 700 “longer life” companies have been founded. The Chan Zuckerberg Initiative — set up by the Facebook co-founder Mark Zuckerberg and his wife, Priscilla Chan — includes in its remit nothing less than curing, preventing or managing all disease by the end of the 21st century.
Is this all pie in the sky and snake oil? “These tech billionaires have often had very quick success early in life,” Ramakrishnan says. “They have this view that life is just some code to be hacked. But ageing is highly complex. There’s a huge amount of hype in the field and a lot of it exploits the anxiety about ageing and dying that we have as humans.”
But amid the hubris, there is hope, he says. “In the past 50 years molecular biology and genetics have made tremendous advances in understanding the processes of ageing.”
So, to go back to his Grim Reaper-ish book title, how do we die? What do we now know about what’s happening in our cells as we do that final mortal-coil shuffle?
Death — if you exclude diseases and inconveniences such as being eaten by a lion — is the result, in simple terms, of ageing. But dying of “old age” seems somehow unsatisfactory. What actually happens inside its victims for life to just stop?
“You can think of ageing as an accumulation of damage to our cells, their ability to function, their ability to talk to one another, their ability to regenerate,” Ramakrishnan says. “Ageing is an accumulation of chemical defects that causes these cells to start malfunctioning.”
When we are young many of the cells in our body naturally rejuvenate. If they become damaged they divide, the mother cell dying off once it has been replaced by its offspring. But one of the markers of ageing is “senescence”. Senescent cells lose the ability to divide and gradually more and more become damaged and die. This isn’t a problem at first. Cells die throughout our life. “We don’t even notice. You could lose an entire limb and still live. But at the point of death you get a critical failure of systems. It’s the ability to function coherently as an individual that’s gone.” Ramakrishnan quotes Hemingway’s The Sun Also Rises, in which a character explains how he went bankrupt: “Two ways. Gradually, then suddenly.” The body ages gradually, then dies abruptly.
Untangling the gradual processes from the sudden — ageing from the final death — is a key focus of longevity research. Which of these processes is down to disease — cancer or Alzheimer’s, for example, which affect many, but not all, of us — and which are simply ageing, which is universal? Separating these factors is where scientists believe they may be close to a breakthrough.
A key hurdle is that evolutionary forces are simply not geared for us to live for ever. “What evolution cares about is for you to propagate yourself, reproduce and pass on your genes,” Ramakrishnan says. “There’s no benefit, in evolutionary terms, to spending a lot of resources trying to live longer.” These forces, however, could be overcome.
Ramakrishnan divides the super-wealthy looking for eternal life into three categories: crackpots, missionaries and rationalists. “The crackpots have these really weird ideas that have no real basis in today’s science,” he says. This includes the field of cryogenics — freezing our bodies upon death until technology advances to the point that we could be brought back to life. “There is not a shred of credible evidence that human cryogenics will ever work.” A twist on this approach is a plan to upload the brain into cloud-based digital storage, to be downloaded into a new life form at a later date. Sam Altman, CEO of OpenAI, is on the waiting list of the San Francisco company Nectome, which is looking to “back up” customers’ minds.
Then there are the missionaries. “These are people who understand some biology and want to use it to do serious life extension,” Ramakrishnan says. Into this category might fall Bryan Johnson, the 46-year-old tech billionaire who hit the headlines last year when he revealed he’d had blood plasma from his 17-year-old son, Talmage, transfused into himself in a process extrapolated from the technique known as parabiosis, the surgical union of two or more bodies. He hoped this would give him the heart of a 37-year-old, the skin of a 28-year-old and the lung capacity and fitness of an 18-year-old — but it ended up just making him look a bit creepy.
Ramakrishnan is sceptical — and Johnson admitted seeing little benefit from the US$2 million-a-year procedure — but studies have shown that the blood of young mice can extend life in older mice. Early findings suggest younger blood reduces the activity of genes that cause inflammation. Isolating factors such as this could eventually help create a treatment that slows the ageing process, Ramakrishnan says.
Undeterred, Johnson’s next wheeze involves the science around telomeres, the protective tips at the end of our chromosomes. During our lives telomeres get shorter each time cells divide, which means they can no longer properly protect chromosomes and cells can no longer divide and replenish. A chemical in the body called telomerase allows some cells to rebuild telomeres, potentially enabling cells to replenish indefinitely. Johnson aims to hijack this process. However, it may also heighten cancer risk as telomerase allows tumour cells to divide indefinitely. If this can be overcome Ramakrishnan believes it could address key parts of the ageing process.
Which brings us to the rationalists, a category in which Ramakrishnan includes himself. This group focuses on tackling disease as a way of extending our lifespan. “For many diseases — heart disease, cancer, dementia — the risk increases with age. So if ageing is a common risk factor, maybe we should be thinking about what we can do to tackle ageing, so we can live healthier lives.”
Ramakrishnan appears fit and still goes on hiking holidays with his wife, Vera Rosenberry, a children’s illustrator and writer from Ohio. But he admits “it sometimes feels that life is like being constrained to a smaller and smaller portion of a house, as doors to rooms that we would like to explore slowly close shut as we age”.
But Ramakrishnan is not, truth be told, interested in immortality. His driving force is to focus on the cellular and molecular processes that govern ageing and disease in the hope that more of us can enjoy good health towards the end of our lives. If the quest for eternal life gets us to that goal, then so be it. “The book is called Why We Die, but it may as well be called How to Live,” he says.
At 71, is he really not tempted by the prospect of utilising the rapidly advancing science of ageing to stretch his lifespan and career? We live long enough already, he says. The danger of ever greater longevity is the creation of a stagnant society, in which the elderly cling on to economic resources and positions of influence. “I’m going to retire next year. I’m still doing OK — my lab is still publishing in good journals. But a 35-year-old could create an entirely new field. It’s a sense of generational fairness. We already live twice as long as our ancestors.”
Of all the billionaires with a god complex investing in longevity, it is Bill Gates, with his anti-malaria mosquito nets and vaccine drives, for whom Ramakrishnan has the most respect. “He’s asking, how can we increase the lifespan in poor countries? The irony is he’s probably doing more to increase human longevity than any of these guys.”
So instead of taking up valuable lab space Ramakrishnan is going to learn languages, read and spend time visiting his children and grandchildren in the US. He hopes to follow the example of his father, who, at 98, still lives fairly independently.
As Ramakrishnan puts it: “While we wait for the vast gerontology enterprise to solve the problem of death, we can enjoy life in all its beauty. When our time comes, we can go into the sunset with good grace, knowing that we were fortunate to have taken part in that eternal banquet.”
Forever young
Could these techniques offer the key to immortality?
Cryogenics
The practice of freezing the body immediately after death, with the aim of defrosting it when science has progressed enough to revive and repair it. Transhumanism, a twist on this, involves storing the brain until its data can be uploaded into a new life form. Only for the very optimistic.
Vampire blood
Scientists have discovered that when two mice — one old and one young — are fused together surgically with a shared blood supply, the elder of the two gets a lifespan boost. When the results of this experiment were published, one US company started selling blood from donors aged 16 to 25 for $8,000 a litre. Researchers are now trying to isolate the beneficial factors in young blood.
Rapamycin
Studies have shown that animals on calorie-restricted diets tend to live longer. Rapamycin — an immunosuppressant drug used to stop organ transplant rejection — holds promise as a way of mimicking the effects of caloric restriction without having to actually reduce your food intake. Such is the hype around the drug that some scientists are said to be quietly self-medicating with the drug. But suppressing the immune system comes with obvious risks.
Cell regeneration
As we age cells are no longer able to divide and replace themselves. These “senescent” cells are the cause of grey hair and many other hallmarks of ageing. Natural substances such as telomerase can trigger cell division, but can also promote cancer growth.
Why We Die by Venki Ramakrishnan (Hodder & Stoughton) is available in New Zealand from June 11.
Written by: Ben Spencer
© The Times of London
