Leon Peshkin monitors his 97 year-old father Miron Peshkin at Hebrew SeniorLife on June 14, 2018. Peshkin is looking for signs of responsiveness in his father to educate his decision on whether to continue life support. (Ruby Wallau/STAT)
Leonid Peshkin calmly strokes his father’s thin, white hair. He gently exercises the old man’s arms to activate his muscles and get the blood flowing. He speaks, voice raised to reach him through the fog of age, poor hearing, and illness. “Papa,” he asks in their native Russian, “are you in pain?”
Almost imperceptibly, Miron Peshkin, age 96 and silenced by a minor heart attack, delirium, antibiotic-resistant infections, and six months of medical care, shifts his head to indicate “no.”
The younger Peshkin, 48, studies the biology of aging at Harvard Medical School in Boston. A broad-shouldered man with a twinkle always lurking in his brown eyes, Peshkin has been obsessed with aging since childhood because he worried that his father — then as old as other kids’ grandparents — would soon pass away.
“How funny it is,” Peshkin said, “that I had to be super worried he was going to die when I was 10. And here I am almost 50, and he’s still around.”
Now, as Miron lies virtually motionless in a nursing home, Peshkin fights his own battles with aging a few miles away, in a fifth-floor lab just off the Harvard Medical School quad.
The lab’s main attraction is a mammoth, glass-fronted incubator stocked with tiny crustaceans called water fleas. Peshkin is raising them to try to understand their natural lifespan. Once he knows how unusual it is for these bugs to survive past the 40 days they typically live at room temperature, he will begin dosing them with drugs to see if he can extend that trajectory.
Peshkin and his parents also contribute to research in a less conventional way. All three have donated their genetic code and cells to science.
Those cells have been altered to reproduce indefinitely. Their usefulness to research will far outlast Miron’s life, and probably his mother’s and Peshkin’s too.
But that’s not what Peshkin’s aiming for, he said, quoting Woody Allen’s famous line about wanting to achieve immortality — not through his work — but by not dying.
That’s why Peshkin continues to fight for his father’s life, despite the increasing futility.
Yes, he understands that his father is old and unlikely to recover. But no, he isn’t ready to stop aggressive medical care, Peshkin has told the chaplain at the Catholic hospital that treated his father, and at the Jewish nursing home where Miron now lies in a world mostly his own.
Peshkin highlights the irony: Persecuted for decades in Russia for being Jewish, Miron has no real faith — except in science. And yet these people of faith want to decide his fate. Plus, Peshkin has come, over the six months of his father’s illness, to doubt the medical care that keeps him alive. Too many times doctors told him his father was gone; only to have him bounce back and become himself once again.
So every day Peshkin drives to the nursing home to stroke his father’s head, stretch his arms, talk to him, and check in with caregivers.
And Peshkin continues to struggle with the question that has haunted him since childhood: Why must his father die?
“It just didn’t make sense the whole idea that you have to get old, your parents, your loved ones have to get old and die,” Peshkin said. “It just made absolutely no sense to me and it still doesn’t.”
A Lifelong Interest in Longevity
Anti-aging research is one of today’s hottest fields. Billionaires donate fortunes to advance work aimed at slowing the hands of time.
But the genesis of Peshkin’s interest in longevity goes back 43 years, to the streets of Moscow.
Walking in the park with his babysitter, they crossed paths with a fancy funeral — big crowd, brass band, bright red open casket. Peshkin doesn’t remember who died, but he does remember the questions it left him with: What is death? Why do we have to die? Why put someone in a box who looks so alive?
His parents had always answered his questions before. But this time, their explanations were inadequate and awkward. Their inability to satisfy his curiosity made as big an impression on him as the funeral.
His father was a scientist, first in the aviation industry and then — when he was kicked out for being Jewish — in the oil and gas business, studying how liquified gas moves through sand. Working for the state, Miron didn’t earn much, so he translated technical documents from German and English into Russian for extra cash. Peshkin’s mother, Klavdia Logvinskaya, worked herself up from lab technician to engineer, researching additives that influence the properties of metal alloys.
They were always demanding of their son. They told Peshkin he had to be 10 times better than everyone else to overcome the discrimination he would face as a Jew.
Growing up, almost all the adults Peshkin knew were the Ph.D.-level scientists who were his parents’ friends. “It was clear that science is the only thing worth doing in life,” he said. As a young boy, a family friend showed him how to memorize a string of 50 facts after just a few minutes of study. “It gave me this idea of power over nature,” he said.
At age 10, after watching some television hospital dramas, Peshkin remembers taking a cord from an old desk lamp and having it at the ready to shock his father’s heart, in case he went into cardiac arrest. “It’s very good he never had a heart attack, because I would have finished him,” Peshkin said dryly.
Peshkin came to the United States in 1995 to attend Brown University, where he trained in statistical machine learning, a type of artificial intelligence, before switching to systems biology. His parents joined him in Boston a decade ago as political refugees, fleeing anti-Semitism.
His mother, sitting in his office recently after a nearby doctor’s appointment, reminds him in Russian that he also promised to build an engine to replace their failing hearts, so they would never die.
He still holds onto that dream of keeping them alive.
“I guess I’m not a very religious man. I don’t think there is some kind of rational design or purpose,” he said. “Even if there is, I’m not ready to accept [it].”
Searching for Clues to Reverse Aging
Some of the most exciting, perhaps fanciful, biomedical research involves slowing the aging process. Research in animals is especially tantalizing. Deprive a worm of calories and it will live longer. A number of drugs extend life in animals and are being studied to see if they can reduce the risk of age-related diseases in people.
Many anti-aging scientists themselves pop supplements or gratefully accept diagnoses of pre-diabetes so they can start taking drugs that have shown promise.
Peshkin’s own research focuses on the water flea, Latin name Daphnia, an insect barely visible to the naked eye. Known primarily as food for aquarium fish, these mostly transparent crustaceans eat algae and protozoa and survive for about 40 days when kept at room temperature. (They live longer in warmer environments.)
It’s that “on average” that troubles Peshkin. No one knows the full range of a Daphnia’s lifespan. So, if a Daphnia lives for 60 days while given a particular drug, is that a potential silver bullet or simply the water flea equivalent of human outlier, akin to his father living to 96? Or if they continue having offspring and resist turning opaque — the water flea version of going gray — does that mean that he’s extended their “healthspan,” which is the true goal of all anti-aging research?
Peshkin said water fleas make a good research species because of their relatively short lifespans, and because unlike flies or worms, they can be precisely dosed with medication. It’s hard to tell how much an individual fly is consuming; worms are very efficient at excreting nutrients they don’t need. Water fleas, on the other hand, have to absorb the medication Peshkin gives them, because they’re swimming in it, he said.
They can reproduce asexually, unless under stress, so all of his Daphnia are identical genetic clones.
He mentioned one cool trick with Daphnia that many middle school sciences classes try: Add caffeine to their water and you can watch their heartbeats speed up. (When Peshkin’s wife was pregnant seven yeas ago, he was worried about her addiction to coffee. He pumped tadpoles full of caffeine during their entire developmental process — and saw no issues in their offspring. His wife remains addicted.)
Last year, before Peshkin’s research funding didn’t come through and his water fleas died, he got encouraging early results from the fleas when he tried them on a drug called Wortmannin, shown to extend the life of fruit flies. He froze one Daphnia every day so he could later examine the genes that were turned on and off during development, and as the animal aged.
Now, he’s starting to build up his colony again in collaboration with Marc Kirschner, the founding director of Harvard’s systems biology department. “Our target is getting a steady supply of old animals. It’s trickier than it sounds,” he said.
He compares his scientific process to the child’s game Twenty Questions. “I use drugs as questions,” he said, interrogating them to see if they can extend the life of water fleas, and therefore, potentially, humans. “I want to find the minimal number of questions that allow you to get an answer.”
Henrietta Lacks 2.0
The human cells used most often in research labs around the world came originally from a Maryland woman named Henrietta Lacks, who died of cervical cancer in 1951. The doctors who treated her did not get her permission before shipping descendants of her cells all over the world. The ethics of that were questionable back then and are certainly unacceptable today.
So when Harvard geneticist George Church set out to amass human genome, health and trait data for research, he made informed consent a huge part of the process.
Miron was the 15th person to sign up for the Personal Genome Project, which now counts hundreds of participants; Peshkin and his mother soon followed. The three don’t share the privacy concerns some people have about making their genetic information public.
“I didn’t invent my genome,” Peshkin said. “This idea that it’s mine in the sense of property is sort of foreign to me.”
His mother said she can’t imagine ways that publishing her genome might hurt her. “This is for science and scientists,” Logvinskaya said in Russian, while Peshkin translated. “Those are not villains. Those are not random people.”
A few years after volunteering their information, Personal Genome Project organizers approached the family with a request: Would they participate in a federally funded effort to develop a standard for genetic sequencing?
Other fields set standards. A cylinder of platinum-iridium alloy, for instance, sits in a basement vault in the U.K., providing the reference weight used around the world for a kilogram.
But when scientists sequence a genome, they have no way of knowing the accuracy of that sequence or whether it’s good enough, because they have no high-quality benchmark to compare it to. It’s that benchmark that the Genome in a Bottle project is working to create, said Justin Zook, a scientist at the National Institute of Standards and Technology and co-leader of the initiative. In addition to the Peshkin family, they’ve now sequenced one pilot genome and one man of Han Chinese descent. They plan to add that man’s parents soon, and eventually others that reflect more ethnic and racial diversity, Zook said.
Peshkin said he briefly contemplated one far-out concern with the project: If his was the reference genome, could his own body become valuable to a scientist who wanted to, say, test an Alzheimer’s drug on the real person it was designed to treat?
“If my brain is the best brain for the experiment because they’ve been working with cells derived from me, maybe there’s suddenly a price on my head,” Peshkin said. “It’s more like a great plot for a movie, and I dismissed it because I thought it’s a very, very unlikely scenario to worry about.”
So he agreed.
Data associated with the Genome in a Bottle samples were downloaded to about 15,000 computers worldwide in 2017, Zook said, suggesting that there’s a strong appetite for the information.
Weirdly, Peshkin won’t be able to study his own samples; it wouldn’t be safe. Like Henrietta Lacks’ original cells, the ones he donated have been modified to reproduce indefinitely, which is essential for their scientific usefulness. But that makes them extremely dangerous to Peshkin himself — and only him. If he comes into contact with his own modified cells, his body won’t recognize them as foreign. “They will keep multiplying and growing on me and eventually will kill me,” he said matter-of-factly.
Privacy vs. Science
The Personal Genome Project is now considering what tissue to collect from Miron when his heart or another organ finally gives out, said Michael F. Chou, a lecturer in genetics and director of human subjects research for the project.
Miron’s gene sequence and tissue will be publicly available and connected with his health records; other gene expression data from tissue has been anonymized. Without that personal data, researchers can’t know if their pancreatic tissue sample came from a diabetic who died of a heart attack in his 50s, for instance, or from someone like Miron, who has lived nearly two decades longer than the average American male.
It may sound morbid to contemplate such ideas. But though Peshkin still sees death as pointless and illogical, it would be even more meaningless in his view to bury an intact body in the ground where it can do no good.
“I think the best we can do is leave our body to science, even though a lot of science is also a waste,” Peshkin said. “I think that science is the best thing we have.”
There isn’t much more time left to make these kinds of decisions.
Over the last two weeks Miron has slipped further away. Peshkin is sure his father, whose 97th birthday is July 9, can still hear him. But Miron is not as responsive as he was, his eyes are less alert, his stare more vacant. Peshkin would have given up already if his father hadn’t bounced back twice before, though he concedes that chances are now slim.
His father’s palliative care team has scheduled a meeting for Wednesday afternoon. Peshkin expects they will pressure him to dial back on Miron’s aggressive medical care, potentially hastening his demise.
He wonders aloud when he will be ready to accept what he still doesn’t think should be inevitable.
“I think I will try to fend it off for a little longer,” Peshkin said.
Correction: An earlier version of this story misclassified Daphnia on first reference and Peshkin’s field of research.
This story was originally published by STAT, an online publication of Boston Globe Media that covers health, medicine, and scientific discovery.
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