We Are All Stardust (Expermiment Publishing, 2015) reveals the voices, stories, and inspirations behind paradigm-changing discoveries, shedding light on the mysteries of existence that we all wonder about from love and beauty to justice and pain.This fascinating collection brings you the stories behind the world’s top scientists—and in doing so discloses to us how closely the science that has shaped our lives intertwines with their own—in and out of the lab.
Molecular Biologist
Elizabeth Blackburn
On Aging
Aging seems to be one of the unpleasant facts of life—though the sixteenth-century French essayist Michel de Montaigne didn’t think so. He wrote, “To die of old age is a death rare, extraordinary, and singular,” granted to only a lucky few in Montaigne’s violent and plague-stricken time.
Today scientists question whether our physical and mental decline is really inevitable. Elizabeth Blackburn is among the pioneers of that research. Born in a small, remote city in Tasmania in 1948, the second of seven children, she studied biochemistry at Cambridge. She went on to investigate the genetic mechanisms of aging. For that work, she received the Nobel Prize in 2009.
In her lab at the University of California, San Francisco, she talks about her discoveries as enthusiastically as if she had just made them. At those moments, you sense behind Blackburn’s friendliness and sense of humor a formidable tenacity. Her gently uncompromising character has not only advanced her career; it also led to her dismissal from President Bush’s council on bioethics in 2004.
They’re marvelous creatures. They can reproduce asexually by simply doubling themselves. Yet they have seven sexes that mate in pairs. And occasionally even three ciliates join to breed. That makes you wonder why we’re content to be women or men— especially since ciliates, regardless of sex, have a choice of seven different types of mating. That’s wild! How can anyone not love those organisms?
Did you suspect that with your investigations of ciliates you were close to solving the mystery of human aging?
No. We wanted to study fundamental questions of molecular genetics. That was exciting enough: In 1975 my later husband and I were among the first people who could read genetic information at all. Ciliates were well suited for those experiments. As my lab made progress over the years, I started to think that we were getting at the heart of biology. But I never had the goal of curing human aging.
Reading the newspaper articles on your 2009 Nobel Prize, one might think that you had managed to do just that. Did you find all the hype excessive?
Not at all. For a long time, I myself couldn’t believe that the discoveries we made about ciliates could be applied to humans. But we’ve since found unequivocal evidence.
Ciliates are immortal.
That’s part of the beauty of their biology. These single-celled organisms can divide endlessly, perpetually beginning a new life. We wondered how they do that. The problem is that a bit of the chromosomes, which contain the genetic information in the cell, is lost with each division.
Eventually they become too short, and the organism can no longer function.
That’s just what the ciliates prevent with an extremely well functioning repair mechanism. Carol Greider, my graduate student at the time, found evidence for that on Christmas Day in 1984: There’s a substance in the nucleus of the ciliates that is able to perpetually rebuild the ends of the chromosomes.
An elixir of immortality for cells.
We called it telomerase. It helps form a sort of protective sheath on the chromosome—the telomere, to which ciliates owe their endless life.
Our bodies can regenerate as well. Our organs too rejuvenate themselves through cell division; their cells, in a sense, produce their own successors. Only that doesn’t happen as often as we’d like.
Exactly. As we age, more and more cells die off without replacement. As a result, our bodily functions deteriorate. But humans have telomerase too. Ten or so years ago, scientists found that in families with members who don’t produce enough telomerase due to a genetic disease, those members suffer unusually early from age-related afflictions. That proved that telomerase delays aging for us as well.
Do those poor people get premature dementia?
Unfortunately, they don’t have enough time for that. They die beforehand of cancers and all sorts of infections—as if their immune system simply runs out of steam. It seems to be related to the fact that their telomeres get too short. Since that discovery we’ve witnessed a tsunami of insights on the connection between aging, diseases, and telomere length.
It’s as if inside each cell were something like a thread of life. In Greek mythology this dictates not only the length but also the quality of our lives.
A nice image. But the development doesn’t always go only in the direction of decline; occasionally telomerase causes the telomeres to grow again.
What determines how well our cells regenerate?
The circumstances of life play an important role—especially chronic stress. In collaboration with psychologists, we studied mothers of disabled children. Often here in the United States they don’t get much support, and they’re under enormous stress. And the more years they took care of their children, the shorter their telomeres tended to be. We found a similar situation among people who had suffered trauma as children, like the death of a parent or even sexual abuse. The greater the number of terrible experiences they had to cope with, the more their telomeres had shortened on average.
As if each blow of fate cut off some of the thread of life.
Stress early in life seems to leave particularly deep traces in the nucleus. These results make one thing quite clear: how critical it is to protect our children. There are people, however, who can get over even great hardship amazingly well.
Apparently, how long we live is also hereditary.
Yes. Fabulous evidence of that is the Gotha, the German almanac of the nobility. In it, the life spans of around five thousand daughters from all over Europe are recorded; those of the sons don’t tell us much because too many of them died at war. The women, on the other hand, almost always led comfortable lives, as long as they survived childbirth and childhood infectious diseases. If you compare the age they reached with that of their parents, you make an amazing discovery: Up to about seventy-five years, the one has little to do with the other. Whoever dies up to that point fell victim by chance to an illness or a misfortune. But whoever makes it beyond her seventy-fifth birthday has her genes to thank: Typically, those long-lived nobles also had particularly long-lived ancestors.
All of us are increasingly in the situation of those noble daughters. Thanks to good hygiene and medical care the likes of which not even queens could have hoped for in earlier eras, most people could easily make it to seventy-five.
Do genes then set a natural limit to our lives?
We might be the first generation that can find out—because we live in an environment more protected than ever before. It’s not what we were selected for in our evolution. Even though lots of people still die of cardiovascular diseases, the number is decreasing; heart attacks can be avoided through a healthier lifestyle. Whether that also goes for the other big killer, cancer, is an open question. How far human life expectancy can be increased is a huge experiment. And all of us are the lab rats.
What’s your hypothesis?
To live to 120 is clearly permitted by the current gene pool of our species. The oldest person up to now was Jeanne Calment from the South of France. She learned fencing at eighty-five, rode a bike at one hundred, and died in 1997 at the age of 122. As is true of most people over a hundred years old, her family members lived to be very old as well. And she enjoyed excellent health all her life— even though she smoked like a chimney!
What did she die of?
It’s unknown. It’s possible that her death had no particular cause, as is the case with so many really old people: Eventually the whole system simply becomes unstable. Then all it takes is a fall or pneumonia and you die. On the death certificate they then write “heart failure.” That way, as a doctor, you’re always right.
Usually, medical science assumes that diseases and not old age lead to death. You make the opposite claim.
What does the word “disease” actually mean? It can mean different things: On the one hand, there are ailments with a clear cause. We’re infected with some bacterium or virus, and the symptoms set in. That’s where medicine has had its great successes. On the other hand, there are cardiovascular diseases, cancer, and adult onset diabetes, which arise from the organism itself and progress over a long period of time. Currently, doctors can usually only help people live with those afflictions—if they can help at all. Our medical establishment focuses too narrowly on the symptoms. The diabetologist tries to deal with your diabetes, the cardiologist with arteriosclerosis, and so on. But underlying these diseases is a more general process: the failure of the body’s own repair mechanisms.
And with your research you hope to find a new approach to those afflictions?
Yes.
Which would be?
The three big killers of the elderly, cancer, cardiovascular diseases, and diabetes, clearly are influenced by the state of our telomeres. To better understand that, we’ve partnered with human geneticists and a big American health care provider. By scouring the medical histories and habits of one hundred thousand people whose average age is about sixty-five, analyzing their genes, and measuring their telomeres, we hope to find out how combinations of environment, lifestyle, and genetic makeup impact health.
People don’t object to their health care provider organization investigating them so thoroughly?
They all signed consents. And we noticed that during some preliminary studies, people came storming in our doors in their eagerness to participate. Some urged us that they were of particular scientific interest because of their CV or daily yoga practice. All of them wanted to find out about their telomeres.
Do you enjoy the role of modern palm reader, who predicts when people will die?
But no one will learn that from me! Telomere length by itself predicts a particular life expectancy only in statistical terms, just as someone with high cholesterol will with greater probability—but far from absolute certainty—suffer a heart attack. It is the combination of many factors that matters. Unfortunately, many people have a hard time understanding statistics.
Because they are understandably not interested in how many out of a hundred patients with a particular telomere length will still be alive in five years. They want to know their own fate.
Especially as it’s so seductively vivid when you imagine that telomere length directly corresponds to biological age!
You’ve cofounded a company with the aim of offering such tests to everyone. Why?
Because there’s a demand for it. Our university lab could no longer manage the volume of inquiries; that’s how it all began. And someone has to be the first to go public. Better we do it right than others do it wrong. That’s why you won’t be able to send in your sample yourself, but only via your doctor.
What good will this do me?
You get information about your body.
But there’s not much I can do with that information. You’ve only just begun to investigate what exactly the state of our telomeres means for our health.
And we don’t claim to know the answers. Everyone who participates is to be informed that their data serves the ongoing research.
The test subjects risk results that can be extremely depressing. Would you want to know that there’s a 90 percent probability you will die in the next five years?
We conducted a preliminary study on that too: No one seemed particularly worried about their test results. Experience with other genetic tests that make only statistical predictions also shows that people are able to deal quite well with the results. If you have short telomeres, that’s just a warning sign to take a closer look—like the check engine light on a dashboard.
Can we do anything as adults to reverse the degradation of our telomeres—or at least stop it?
Our studies on that are still in their infancy. One thing, at least, is clear: People who exercise more and sleep better have longer telomeres.
Do you know the length of your telomeres?
Yes. I’m not worried. I’m okay.
Have the results changed your lifestyle?
No. But since the results of research on telomeres in people started coming in, I’ve tried to exercise thirty minutes a day. That’s the only magic bullet against physical decline that I accept. The evidence for it is compelling.
Just exercise? That makes you a minimalist. Even leaving aside the billion-dollar nutritional supplement industry, scientists advocate a whole range of prescriptions to combat aging: less sugar, more red wine, vitamin E, green tea. . . .
Everyone takes what seems helpful to them. But unfortunately, no one can ever prove the effects. No one knows how polyphenols, the substances in red wine and green tea that are supposedly so beneficial, really work—or whether they work at all. High amounts of vitamin E can cause cancer. I’m sure it’s sensible to avoid eating too much sugar. But quality of life is important to me, too.
You’re sixty-three. Do the signs of aging bother you?
I find my age excellent. When I was your age . . .
. . . forty-six . . .
. . . I was the mother of a young child. At the same time, my research made extremely heavy demands on my time and energy. I was horribly stressed. Besides, I now have a broader perspective on the world. I wouldn’t want to trade places—even if I was a better skier back then.
Many people find it humiliating that their skills diminish in old age and their looks aren’t what they used to be. Women in particular suffer as a result of that.
But it doesn’t have to be that way. Women can bloom again when the kids are out of the house. For that they need support, however. Unfortunately, it’s still common in our society that older women aren’t valued.
You can hardly complain about that—with all the honors you’ve attained.
In the United States, Nobel laureates are no great rarity—but female Nobel laureates are. When I appear in public, lots of people get really excited and want their children or grandchildren to see me. The mere fact that I exist sends a message that women can achieve things of this significance. So I realized at some point that I don’t have to do anything else to be useful. It’s enough to stay alive.
Would you like to live to be 120 or even 200?
Oh, yes! But you have to think about what age you want to stretch out. I would gladly turn down the prospect of extending the stage between eighty and ninety. Most people would probably like best to increase the time between twenty and thirty.
Not me. Too much lovesickness.
On the other hand, in those miserable years, we’re at the height of our mental capacity. If I really think about it, I’d like to start over repeatedly with a twenty-year-old brain. First I would spend twenty-five years redoing what I did. Then I’d try to master mathematics and go into cosmology. In cosmology there are such exciting open questions that I sometimes think: Why are you wasting your time with biology? I would play piano more often. And go skiing a lot more.
Leon Kass, the chair of the council on bioethics, of which you were a member, found such dreams disturbing. It is precisely transience, he argued, that has brought out the best in human beings: engagement, seriousness, ties between parents and children. What did you reply to him?
That short life is damned inconvenient. My colleague assumes that, with the prospect of more years, people would become lazy. But can he prove that? I certainly don’t know what in my vision of three successive careers suggests a lack of seriousness. However, I’m not saying that my model works for everyone. Some people would be worried that they’d have to be married to the same person for 180 years!
But the question is what the point of aging is in the first place. Turtles, for example, are spared that fate.
In what way?
Not even an expert can tell the difference between the organs of a young turtle and those of a hundred-year-old turtle.
Apparently, those amphibians have extremely efficient repair mechanisms. In evolution, different reproductive strategies have prevailed. An animal can either reproduce mainly in its younger years, as we do, in which case a longer life offers no biological advantage, or it can produce offspring until it dies, as the turtle does, in which case each year is a gain. However, it costs the organism a lot of energy to constantly stave off decline.
Food might have been scarce for our ancestors, but it’s not for us. Would it be conceivable to improve human metabolism to the point where we wouldn’t age anymore either?
In theory, yes. We could become immortal. The only question is whether our cellular machinery would be adequate. It’s possible that the system we’re born with would eventually reach a point where nothing else could be tweaked.
Where might that be?
We don’t know. I’m on the advisory board for an initiative called Tara Oceans, which is attempting to study all the life in the ten meters under the ocean’s surface. People find the most amazing creatures there—such as copepods with incredibly well-functioning repair systems. Even though they’re multicellular organisms, some of them might even be immortal.
It’s not a law of nature that higher life moves inexorably toward death.
No, it’s not.
Are you afraid of death?
Not anymore. My son is grown up. I’d feel sad for my husband and him if I passed away. But a lot of good things have happened in my life. Why should I fear death?
Excerpted from We Are All Stardust by Stefan Klein. Reprinted by permission of the publisher, The Experiment. Available wherever books are sold. theexperimentpublishing.com
