“Shalom, Professor, thank you for agreeing to see us. I’ll get straight to the point. Can stem-cell transplants cure people who are ill?”
“Yes: we dream of treating Alzheimer’s, Parkinson’s, diabetes, leukaemia … Here, we create iPS cells to regenerate the placenta in some pregnant women.”
“So, if you inject me with stem cells induced from me, could I live to be five hundred?”
“You’re not ill: I might just as easily give you cancer at the site of the injection. That’s the problem: iPS cells are unstable, sometimes aberrant. Given what they do to mice, imagine what they would do to you: a guaranteed tumour.”
“So when will people be able to live to be three hundred?”
“I thought you were aiming for five hundred.”
“I’m happy to lower my expectations to two-fifty or even two hundred.”
Romy, who had her whole life ahead of her, was profoundly bored by this conversation. To a ten-year-old girl, the idea of living to be two hundred is as tedious as having to watch a 52-minute documentary on the glories of the Chateaux of the Loire Valley with Lully’s Marche Royale on the soundtrack. Doctor Buganim addressed himself specifically to her, forcing himself to use words that would be intelligible to a little girl. You could tell he was a veteran of medical conferences. One of the most time-consuming aspects of techno-medicine is persuading the rich to provide funding at medical conferences; researchers have to hard-sell their discoveries to pay for their test tubes. He had been prepared to meet with me because I had led the hospital’s PR department to believe that I was a major French TV journalist. He was hoping that my fame would provide him with some crumbs he might use to save the rest of humanity.
“Miss Romy,” he said, “let me explain how you came to be here. First a sperm fertilizes an oocyte, and this produces and egg called a zygote. This single cell begins to divide: two, four, eight, sixteen. When it reaches sixty-four cells, it becomes a precursor to the embryo, called a blastocyst, and looks like a hollow ball. When scientists cultured these cells, they discovered that they replicated themselves indefinitely and continued to remain identical.”
Romy was spellbound. I prompted him, just as my mentor Yves Mourousi prompted me.
“A colleague of yours told me that some cells are immortal.”
“Yez. Ze embryonic ztem zellz are immorrrtal.”
I forgot to mention that we were speaking English. Romy was having a hard time following Doctor Buganim, and I was having a hard time taking him seriously, since his Israeli accent reminded me of Adam Sandler in You Don’t Mess with the Zohan, the best comedy about Israel I’ve seen. To avoid bursting out laughing in such a situation, it was essential for me to ignore his accent and focus on the fact that, in twenty years working in television, I had never been awarded a prize by Science.
“Embryonic stem cells are immortal,” he had just calmly announced.
“So, the cells are like chameleons?” Romy said, astounding her co-interviewer.
“Exactly. They can become anything you want them to be. Well … almost anything. Hence their name: pluripotent.”
On a whiteboard, he drew a round cell that looked like Les Shadoks (another outmoded reference).
“Tell me about the Japanese scientists who first discovered how to create stem cells. What is the iPS system?”
“Careful. They’re not just stem cells, they’re embryonic stem cells. That is to say, cells capable of generating any kind of cell within the human body. As adults, we all have stem cells in our organs. Romy does too. But they only know how to regenerate the cells of that specific organ. The Japanese scientists wondered whether it would be possible to take adult cells and reprogramme them to become embryonic—meaning pluripotent—stem cells. This would address two issues: 1) the ethical problem: the idea of destroying human embryos is not pleasant, even though I’m not sure that I would consider the blastocyst—a microscopic ball—as being alive; 2) transplant rejection: if I inject you with embryonic cells from someone else, they will almost certainly be rejected. On the other hand, cells taken from your own body, collected from a skin biopsy, will not be rejected.”
He was scratching under his arm. Romy turned to me, worried.
“He’s not going to give us an injection, is he?”
“No, no one is going to do anything to you, chérie.”
“But even if I did,” the researcher said, “it’s just a little scratch on your arm, it doesn’t hurt.”
“If I understand what you’re saying, the Japanese scientists collected adult cells and managed to … rejuvenate them?”
“Exactly. That’s precisely it. I collect your skin cells, I introduce a few transcription factors, wait two or three weeks, and suddenly we see “induced” embryonic cells—that’s the ‘i’ in ‘iPS.’”
“That’s insane!”
“Completely insane! No one believed it could be done. Certainly, no one imagined that it would take only four genes. There are 20,000 in the human body. And it takes only four to travel back through time. The British scientist John Gurdon deserves some credit for the discovery—he was the first person to reprogramme cells. He shared the Nobel Prize with Shinya Yamanaka in 2012. He was the man who first devised the technique that was later used to clone Dolly the sheep. Gurdon took a frog zygote, collected DNA from a tadpole’s intestinal cell and, by introducing the DNA into the enucleated egg, produced an embryo. If you take the nucleus of an adult cell and introduce it into an enucleated zygote, it produces a clone. The egg begins to divide: two cells, four, eight, etc. Using his system, anything can be cloned.”
“Anything? You mean I can be cloned?” Romy shrieked.
I was amazed that my daughter could understand his English despite the heavy Israeli accent.
“Not like in Star Wars, but we can create a genetically identical Romy. I take a skin cell from you, extract the DNA, and insert it into an enucleated human egg, let it grow for a few days, implant the embryo into a surrogate mother, and nine months later, we’ll have a clone, a baby genetically identical to you.”
Romy was really starting to panic now; I decided to intervene to avoid any further trauma.
“Nobody’s going to clone you, darling—it’s exhausting enough having to cope with one Romy. It’s strange, Doctor. Fifteen years ago, everyone was obsessed with human cloning but no one really talks about it anymore. Has it gone out of fashion?”
“It’s not about fashion, as you put it. Human cloning is prohibited for ethical reasons. But I’m sure someone, somewhere in China, is working on it.”
“You really think so?”
“I don’t think so, I’m certain of it. They’ve already cloned pigs, dogs, horses … The first successful human cloning was done in 2013, by Shoukhrat Mitalipov, a Kazakh-born American professor at the Oregon Health & Science University in Portland.”
“But there was no mention of that anywhere!”
“Yamanaka’s discovery made his approach obsolete … for now.”
“So, in your lab, do you use cloned mice or genetically reprogrammed mice?”
“Both. In 2009, the first mouse entirely made of reprogrammed cells was born. It was born alive, viable, and capable of reproduction. In 2011, scientists generated a functional larynx, in 2012, a thyroid gland. Eighteen months ago, a mouse liver was artificially recreated using induced pluripotent stem cells. IPS cells are amazing, the only problem with them is that only thirty percent are capable of generating a viable mouse. The vast majority of iPS cells produce embryos that are malformed or miscarried during pregnancy; not all iPS cells are viable. Whereas, if you take the actual embryonic stem cells of a blastocyst, almost all of them can successfully produce a cloned mouse.”
“I don’t understand. I’m talking about extending my life expectancy, and here you are singing the praises of cloning …”
“No. I’m just tryi
ng to explain that we haven’t yet discovered the ideal conditions for cell regeneration. The concept is a solid one, but we do not yet have the means. The goal of cloning, and of genetic reprogramming, is to go back to square one. We call it a ‘reset.’”
“I want a reset, Doctor! It’s time to reboot me! Beigbeder 2.0!”
By now, Doctor Buganim was completely convinced that I was deranged. Romy, meanwhile, was playing Brick Breaker on her mobile phone. In a way, I found this reassuring: knocking down the red brick wall on her iPhone was more important to her that finding out how to reset our lives.
“So, if I understand you correctly, Professor, neither human cloning nor genetic reprogramming can grant immortality.”
“You’re right. A clone will be an exact copy of you, but first it has to be brought to life: nine months of pregnancy, birth, rearing, food, everything starts from scratch. The clone will look like you, but it will never be you. In any case, we don’t use the term ‘cloning’ anymore, it’s too controversial. We prefer to say ‘somatic cell nuclear transfer,’ although in practice the two are exactly the same.
“Dolly the sheep was cloned back in 1996. Since then, science has moved on; now we’re trying to generate a maximum number of high-quality rejuvenated cells that can be safely reimplanted.”
“But you just told me that if you injected me with iPS cells, I’d end up with a tumour. So, I’ll pass, thanks!”
(He laughs) “Imagine you have Parkinson’s disease, you’re constantly suffering from tremors, and I inject you with genetically modified neurons that lessen the symptoms. You’ll be thrilled, even if it means that, ten years later, you might develop a tumour. Here we have discovered four genes (Sall4, Nanog, Lin28, and Esrrb) capable of producing better-quality iPS cells. At the moment, they work on cloned mice.”
“And that’s why you were awarded a prize by Science.”
“Exactly. We’re testing different factors to those used by Yamanaka.”
“So why does it take three weeks, when an egg only takes three days?”
“Reprogramming is slower than programming! Besides, during that time there may be aberrant genetic mutations; we have to be able to control the process.”
“So, immortality is a long, arduous process.”
“I’m not looking to achieve immortality. I’m looking to collect a dermal cell from a patient with Parkinson’s or Alzheimer’s, and to reprogramme it to create a neural iPS cell so that I can study how neurons are affected by these conditions. By studying these genetically rejuvenated neurons, I might be able to treat such conditions. Develop new drugs that can eliminate these diseases. And there’s another possibility: regenerative medicine. We can try to repair the defective neuron and reimplant it into the patient’s brain.”
“Aha. Now we’re getting somewhere. This has something to do with the discovery made by two researchers in 2012? CRISPR-Cas.9?”
At this point, I’m worried I may have lost even my most determined readers. Let’s do a brief summary of the current state of genetics: in 2012 (an important year, since it was also the year that Yamanaka won the Nobel) two biologists, Jennifer Doudna (from California) and Emmanuelle Charpentier (from France), developed a technique that allowed them to splice DNA and reintroduce the modified PD1 gene. Having noticed palindromic repeats (that is to say, inverted repeats of the letters A, C, T, and G) when sequencing bacterial DNA, they gave it the acronym CRISPR (clustered regularly interspaced short palindromic repeats). Don’t ask me to explain how they did it, it would take me ten years of study to even begin to understand. The two researchers used CRISPR to insert a gene into the DNA. “Cas.9” is the name given to the protein used in the operation. This new technology has significantly simplified human genetic modification. Yossi Buganim was amazed that I was aware of these scientific developments, when actually, I’d simply asked my assistant to prepare a crib sheet before my trip. He now talked without any attempt at simplification, as though he was chatting to a colleague at the Annual J.P. Morgan Healthcare Conference in San Francisco.
“Imagine the mutant DNA of a patient with Parkinson’s,” he says, “In theory, we can treat the patient using the CRISPR method and introduce new DNA. Using the Cas.9 protein, guided by RNA, we cut DNA and perform the modification. We use this technique every day now.”
“Aren’t you terrified at the thought of creating a GMH (genetically modified human)? The Americans, the Chinese, and the British have recommended a moratorium on human genetic engineering.”
(He smiles) “In China, Doctor Lu You, at Chengdu University, is using CRISPR to modify T-cell lymphocytes in patients suffering from metastatic lung cancer unresponsive to chemotherapy. They take a blood sample, collect the patient’s T cells, and alter the DNA of the PD1 gene that “protects” the cancer. By reinjecting these genetically modified cells, they believe that the PD1 gene can no longer instruct the T cells not to attack the tumour.”
“So, these experiments are actually taking place right now?”
“Yes. They’ve started human testing. In theory it might work, but at the same time, since the cells are no longer sending out signals saying ‘do not attack,’ there’s a risk that the genetically modified cells will attack healthy cells … creating the risk of autoimmune disorders.”
“Why aren’t you doing experiments like this here in Jerusalem?”
“It’ll take us years to get permission. In the US, a similar immunotherapy trial on patients with leukaemia (called the “ROCKET trial”) was discontinued after five patients died. And then there are the tragedies caused by quack doctors. A Russian family living here in Israel, whose son had a neurodegenerative disease, paid a fortune to have him injected with stem cells in Kazakhstan. When the boy came back, he had to be admitted to the emergency unit at Sheba Hospital: they found two brain tumours. He died shortly afterwards.”
“So, you’re saying that only Western scientists are respecting the moratorium?”
“Yes. But if someone from India, Russia, Mexico, or China offers you a miracle cure, be very careful: there are no medical controls.”
“In Switzerland, I found an online clinic that injects stem cells taken from sheep foetuses!”
“I hope what they’re injecting are placebos, otherwise they could kill you. In China, fifty years from now, people will be demanding blond, blue-eyed children, and people will be able to supply the demand.”
“With the legacy of the one-child policy, they haven’t got enough women: now they’ll be able to create Barbie dolls to order!”
“Or clone vicious animals, or engineer super-soldiers. Or uncontainable bloodthirsty monsters.”
“We’re getting close to the Nazi dream—the creation of a super-race.”
“Exactly. The researchers here work to make pluripotent stem cells. We were the first lab to create iPS cells from placenta. And also single cells, called totipotent cells, which can differentiate into nearly all cells—though that study hasn’t yet been published. Embryonic stem cells are injected into a blastomere and produce new cells capable of becoming placental cells. These cells occur much earlier in embryonic development than those used by Doctor Yamanaka. We’ve managed to go farther back in the process of gestation. We’re not looking to clone human beings, or to create a superman. We’re simply looking to treat people who are ill, but this will take time.”
Doctor Buganim glanced at his watch. I suddenly remembered that I wasn’t on the set of my TV show but in the consulting room of one of the world’s most prestigious biochemists. I felt it was time to leave the researcher to his research. As he walked us to the lifts, Doctor Buganim tried to reassure me—though the way he went about it was strange.
“Maybe in two or three hundred years, we’ll be able to slow the aging process. But I think the Earth will have died before then. Given the way we treat the environment, within a hundred years the problem will have been solved: the
whole planet will die, and humanity will die along with it. So, there’s no need to worry about immortality. Now, if you’ll excuse me, I have mice to exterminate.”
“Ah, Jewish humour!”
Thankfully, Romy hadn’t heard a word: she was involved in a game of Angry Birds.
-
ATHEISM IS A religion like any other. Its one original concept is that heaven and hell are the same place: here. There is no afterlife; not even in celestial Jerusalem. The point-blank objections of the Israeli researcher had not discouraged me. Was I possessed by some kind of supernatural geographical contagion? Anyone who has not set foot here cannot understand why so many people fought for thousands of years to conquer this city. Another taxi ferried us back downtown, to a wall of pink stones hidden behind a bus queue.
“Are we going to visit the three gods?”
Romy had insisted on seeing the old city; like all children, she was hungry for magic. I was hungry for a good shawarma with hummus, fresh pita bread, minced lamb, and chopped parsley. I thought, let’s go visit King David’s city: four thousand years of bullshit metaphysics and the Crusades is like catnip to spiritual tourists. Jerusalem is the least secular city on the planet. A religious hypermarket: there’s something for everyone here. As we passed through the Old City walls, built by Suleiman the Magnificent, walking along cobblestones worn smooth by rapturous hordes of sandals, we quickly became lost in this labyrinth of the three monotheistic religions. I booked a table at a Palestinian restaurant.
“The Coke here tastes funny,” Romy said.
“Maybe it’s kosher?”
The passageways were covered, I had never imagined Jerusalem as a maze of vaulted passageways, stone walls with no windows, narrow alleys as crooked and crowded as the metro station at Châtelet–Les Halles at rush hour, and a lot dustier. Romy insisted that I buy her a “SUPER JEW” T-shirt that I told her she can’t wear back in France (too risky). As we left the restaurant, we realized that we were near the Wailing Wall. As good a place as any to start our tour. But we were refused entry to the site because: 1) I had to wear a yarmulke; and 2) Romy is female. We turned our backs on the wall to take a selfie together. Then I found a disposable cardboard yarmulke that kept being blown away by the wind, forcing me to run and pick it up from the sand. I think many true believers would have happily had me crucified. I told Romy to wait for me on the other side of the barrier, to the right of this section of wall, while I went down and formulated a wish.
A Life Without End Page 10
