BBC Future's reporter talks about families facing an unexplained illness in their children and a scientist hoping to find a clue to immortality.
Richard Walker began fighting aging as a 26-year-old American hippie. It was in the 1960s, when youth ruled the ball: the time of protests against the Vietnam War, psychedelic drugs and the sexual revolution. Young Walker was tormented by the realization that aging would sooner or later take away his vitality. One evening, driving out in his convertible, Richard promised himself that he would find a way not to age - until he turned 40.
Walker became a scientist to understand why he is mortal. “Of course, the reason was not in original sin and not in God's punishment, as the nuns taught me from the catechism,” he said. "No, we are talking about the result of a biological process, which means that it is controlled by some mechanism that we are able to understand."
Scientists have published several hundred theories on aging, linking it to a wide variety of biological processes. However, no one was able to piece together all this disparate information.
Now 74 years old, Walker believes that research into the causes of a rare disease known as Syndrome X can teach us how to stop aging. He found four girls with this disease, which is characterized by a permanent state of infancy, a stop in development. In his opinion, the cause of the disease was a genetic failure. Finding it means getting close to solving immortality, Richard is sure.
Will not cure
In 2004, when Mary-Margrethe Williams began laboring, and together with her husband John, they went to the hospital, nothing foreshadowed trouble. Their daughter Gabriela was born weak and bluish. In the neonatal intensive care unit, doctors managed to stabilize her condition, after which a whole series of tests began.
A few days later, the Williams already knew that the genetic lottery turned out to be unfavorable to Gabby. The frontal lobe of her brain was smooth, there were no grooves and convolutions, inside which neurons are compactly located. Her optic nerve, which connects the eyes and the brain, was atrophied - this promised the girl blindness. She also had two heart defects and her tiny fists were impossible to open. A cleft palate and impaired swallowing reflex meant that Gabby had to be fed through a tube in her nose. “They began to prepare us for the fact that she probably would not go home with us,” says John. The family priest came to the hospital to baptize the girl.
Every day Mary-Margrethe and John were torn between the hospital where Gabby was lying and the house where her older sister, 13-month-old Sophia, was waiting for them. Tests for genetic syndromes known to doctors gave a negative result. Nobody knew what was in store for the girl. Gabby's Catholic family could only trust in God. “Mary-Margrethe kept repeating that Gabby was coming home,” recalls her sister Jenny Hansen. And after 40 days, she really went home.
Gabby cried often, loved to be picked up, and ate every three hours - just like a normal baby. Which she certainly wasn't. Her parents constantly took her to specialists - to a cardiologist, gastroenterologist, geneticist, neurologist, ophthalmologist and orthopedist. All the experts said the same thing: nothing can be done.
Gabby's hair and nails grew, but she herself did not grow. Its development took place almost imperceptibly, at its own special pace. Mary-Margrethe vividly remembers the day she drove Gabrielle in a wheelchair down the skylight hallway. She looked at the girl and was surprised to find that Gabby's eyes react to sunlight - that is, she is still not blind.
Despite the difficulties endured, the couple decided that they would like to have more children. In 2007, Anthony was born to them, and the next year Alina appeared. By this time, the Williams stopped dragging Gabby to the doctors, accepting for themselves as a fact: the girl will never be cured. “At some point, we just decided,” John recalls, “it's time to come to terms.” Later, two more children were born in the family.
When Walker began his scientific career, the female reproductive system became a model of "pure aging" for him: even in the absence of disease, female ovaries gradually cease to function at the onset of menopause. He investigated how nutrition, light, hormones, and brain chemistry affect fertility in rats. However, fundamental science is the lot of those who are in no hurry. Richard was unable to find a cure for aging either by the age of 40, or even at 50 or 60. His life's work did little to answer the question of why we are mortal. Time worked against the scientist.
It only remained to start from scratch. As Walker writes in his book Why We Age, he embarked on a series of thought experiments on the known and unknown facts about aging.
Aging is usually defined as the progressively accumulating damage to cells, organs and tissues that predetermine the physical changes that are characteristic of older people. What, Walker wondered, if cell damage is the result of aging, not its root cause?
This idea was ripening in the head of the scientist until October 23, 2005. In the evening he was working in his home office when his wife called him into the living room. She thought that Richard would be interested in a TV show about a girl who seems to be stuck in time. Brooke Greenberg was 12 years old, but she weighed only 6 kg, and her height was only 69 cm. The doctors who observed her had never encountered such a disease and believed that the reason lay in an accidental genetic mutation. “Brooke is a real source of eternal youth,” said her father, Howard Greenberg.
Walker was intrigued. He has heard of other genetic diseases, including Hutchinson-Guildford disease and Werner's syndrome, which cause premature aging in children and adults, respectively. However, this girl had a genetic disease that stopped her development and with it, Walker suspected, the aging process. In other words, Brooke Greenberg could help him test his earlier theory.
Brooke was born a few weeks ahead of schedule, with multiple birth defects. The pediatrician called her condition "Syndrome X" because he could not understand what he was dealing with.
After the telecast, Walker found Howard Greenberg's home address. Two weeks later, the scientist received a response, and after much discussion, he was allowed to work with Brooke.
Walker's analysis showed that Brooke's organs and tissues developed at different rates. Her mental development, according to standardized tests, corresponded to the age of 1-8 months. Her teeth were like those of an eight-year-old, and her bones were like a ten-year-old. She lost her infant fat reserves, her hair and nails were growing normally, but she did not reach puberty.
All of this was indicative of "inconsistent development," in Walker's terminology. Brook's body, he said, did not develop as a single whole, but as a set of separate elements that were not coordinated with each other. “She's not quite 'stuck in time,'” Walker wrote. "Its development continues, albeit inconsistently."
Aging, in his opinion, occurs because human development involves constant change. From birth to puberty, change is vital to help us grow and mature. However, from the moment we grow up, our bodies do not need to change - rather, to maintain them in their current state. “Once you've built the perfect home, there comes a time to stop laying bricks,” Walker explains.
Brooke was not like everyone else: it seems that she was born with a "built-in" switch, and it was originally off. However, finding a genetic cause for this has proven difficult. Walker needed to completely decode Brooke's genome.
This was not destined to happen. To Walker's great disappointment, Howard Greenberg abruptly cut off all contact with him. The Greenberg family did not publicly announce their reasons for ending their relationship with Walker, and declined to comment for this article.
One more chance
In August 2009, Mary-Margrethe Williams saw a picture of Brooke on the cover of People magazine, entitled Heartbreaking Mystery: 16 Year Old Baby. She thought Brooke's story was a lot like Gabby, so she contacted Walker.
After looking at Gabrielle's data, Walker shared his theory with her mother. Genetic testing on the girl could help him fight aging-related diseases - and possibly aging itself, he said.
For several months, John and Mary-Margaret weighed the pros and cons. They had no illusions about Walker's research - rather, they were interested in why Gabby was born this way. The Williams couple were firmly convinced that God had sent them Gabby for a reason. Participation in the scientist's work gave them some consolation, because this increased the chances of finding a cure for Alzheimer's disease and other age-related diseases.
By agreeing to participate in Walker's research, the Williams, like the Greenbergs before, gained prominence. However, the life of a Gabby-local celebrity has changed little. The girl is constantly surrounded by members of her large family. She usually lies on the floor or on one of the special pillows designed to keep her spine from curving like a C. She makes sounds that would make a stranger nervous: mooing, noisily drawing in air, grinding her teeth. Her brothers and sisters are oblivious to this.
Together with geneticists from Duke University, Walker tested the genomes of Gabby, John, and Mary-Margret. They studied exome - sequences encoding protein molecules and making up 1-2% of the genome. Comparing the exomes of all three, the researchers concluded that Gabby did not inherit any exome mutations from her parents - which means that her siblings are unlikely to be able to pass her disease on to their children. “It’s a huge relief - a tremendous relief,” recalls Mary-Margrethe.
However, checking the exome did not give scientists any information about the causes of the girl's illness. The genome of each of us contains mutations. Based on the genetic material of one person, it is impossible to understand whether this or that mutation is dangerous - for this it is necessary to compare at least two people with the same problem.
Luckily for Walker, his popularity in the media helped him find two other girls who he believes have a similar condition. An interesting fact is that all known cases of "Syndrome X" occur in girls. This may mean that the desired mutation occurs on the X chromosome - or it may be just a coincidence.
Walker is partnering with a commercial organization in California to help him compare the complete genomic sequences of all three girls - the exome and the remaining 98% of the DNA code believed to control the expression of genes encoding protein molecules.
Most researchers agree that the search for genes responsible for the onset of "Syndrome X" is justified, since these genes will undoubtedly help us learn more about human development. However, they are not at all convinced that the girls' disease is directly related to aging - or that they suffer from one disease. But even if this is so, and even if scientists led by Walker can establish the genetic cause of the disease, it will be a long time before people have the opportunity to take advantage of their discovery.
End of life
On October 24, 2013, Brooke died at the age of 20. Mary-Margrethe was informed of this by a friend who read about the girl's death in a magazine. The news came as a shock to the woman. “Although we never met her family, they literally became a part of our life,” she says.
Gabrielle is doing well. Mary-Margrethe and John stopped planning her funeral and began to think about what would happen if the girl outlived her parents. They do not need a magic pill for old age, they are waiting with interest for her arrival, because these are new joys, new difficulties … And new opportunities to understand something about this life.
Richard Walker's view of old age is, of course, quite different. Answering the question why he is so tormented by the idea of aging, he explains: as a child, he was sad to observe the physical and psychological degradation of his grandparents. “I was not at all happy with the sedentary elderly, rocking chairs and stuffy houses with old-fashioned decorations,” says the scientist.
If his hypothesis is correct - who knows, maybe one day it will help prevent disease and lengthen the lives of millions of people. However, Walker understands too well that he will not have time to help himself. As he writes in his book: "I feel a little like Moses, who wandered in the desert for most of his life, and then was able to see the Promised Land, but never got into it."