China’s Already Tested CRISPR on A Human, and the U.S. Is Next
The first clinical trials on humans of CRISPR-Cas9-edited genes has begun in China.
You probably know about CRISPR-Cas9. It’s the recently developed method for genetic engineering that’s brought costs down by 99%, and the time it takes to modify genes from years to weeks. For some people, it’s a thrilling gateway to a disease-free future, increased lifespans, and babies made to order. (Also featherless chickens and invisible frogs.) To others, it’s a terrifying development with the potential for unstoppable bio-weapons, a corrupted human genome, and babies made to order. The ethical issues of working out CRISPR’s bugs on humans has been an area of universal concern and caution, but now a group in China has announced that on October 28 they modified a living human’s genes for the first time anywhere using the method. And it’s about to be done in the U.S.
Permission to proceed with both of these Phase 1 clinical safety trials was officially granted by each country in July 2016 in what may be an indicator that the temptation to proceed with such a potentially powerful therapeutic tool is too hard to resist, even balanced against the fear of something going wrong or misuse. “The technology to be able to do this is incredible,” Naiyer Rizvi of Columbia University Medical Center in New York tells Nature. Palermo University’s Antonio Russo is hopeful, saying, “It’s an exciting strategy. “The rationale is strong.”
Immunologist Carl June, the scientific advisor for America’s upcoming trials, told Nature his feeling about China’s groundbreaking first step: "I think this is going to trigger ‘Sputnik 2.0’, a biomedical duel on progress between China and the United States, which is important since competition usually improves the end product.”
As a reminder that CRISPR is still a work in progress, the Chinese trial was supposed to take place in August but had to be pushed back due to unexpected difficulties in culturing and amplifying the required cells.
The patient in the Chinese trial certainly had little to lose. A team of doctors at Sichuan University’s West China Hospital in Chengdu, led by oncologist Lu You of Sichuan University, injected him with a CRISPR cocktail that’s was concocted to halt an aggressive form of lung cancer from which he’s suffering. Lu reports that the procedure seems to have gone well, and that the patient has another injection ahead of him.
West China Hospital (WASTON MEDICAL)
Lu’s team plans eventually to treat nine other people in the trial, each of whom will receive either two, three, or four injections. All of the patients will be monitored for six months to see if any adverse effects appear. A team at Beijing University plans to follow up in March 2017 with CRISPR-derived safety trials for bladder, prostate and renal-cell cancers.
“Cell therapies for cancer are so promising, but the majority of people who get these therapies have a disease that relapses,” Edward Stadtmauer, a physician at the University of Pennsylvania in Philadelphia tells Nature regarding the upcoming U.S. trials.
The U.S. trial won’t be so much about treating cancer as trying to verify that CRISPR is safe for use on people, with patients from California and Texas. Facebook Sean Parker’s $250-million immunotherapy foundation is funding the trial.
Launch of the Parker Institute (JONATHAN LEIBSON)
The CRISPR-modified cells will be manufactured from patients’ own T cells by the University of Pennsylvania. Three edits will be made. First, a gene will be inserted for an engineered protein that finds cancer cells and tells the T cells to target them. A second edit removes a naturally occurring T cell that could interfere comes next. The final edit plays defense: It removes a gene producing a protein that allows cancer cells to identify the T cells as immune cells they have to destroy. Each patient will then receive back his or her edited T cells via infusion. Monitoring of the patients for ill effects will follow.
Regardless of how you may feel about the benefits and/or dangers promised by CRISPR-Cas9, it’s clear that the age of CRISPR-edited humans has now begun. Breathe deep and hang on. Human existence is about to get much better, much worse, or both. As Paul Simon’s song “Boy in the Bubble” says:
These are the days of miracle and wonder
And don’t cry, baby, don’t cry
Upstreamism advocate Rishi Manchanda calls us to understand health not as a "personal responsibility" but a "common good."
- Upstreamism tasks health care professionals to combat unhealthy social and cultural influences that exist outside — or upstream — of medical facilities.
- Patients from low-income neighborhoods are most at risk of negative health impacts.
- Thankfully, health care professionals are not alone. Upstreamism is increasingly part of our cultural consciousness.
Researchers hope the technology will further our understanding of the brain, but lawmakers may not be ready for the ethical challenges.
- Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.
- They hope the technology will advance our understanding of the brain, potentially developing new treatments for debilitating diseases and disorders.
- The research raises many ethical questions and puts to the test our current understanding of death.
The image of an undead brain coming back to live again is the stuff of science fiction. Not just any science fiction, specifically B-grade sci fi. What instantly springs to mind is the black-and-white horrors of films like Fiend Without a Face. Bad acting. Plastic monstrosities. Visible strings. And a spinal cord that, for some reason, is also a tentacle?
But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.
What's dead may never die, it seems
The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. Think a dialysis machine for the mind. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.
BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.
The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.
As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.
The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.
"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.
An ethical gray matter
Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.
The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.
Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.
Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?
"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."
One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.
The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.
"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.
It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.
Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?
The dilemma is unprecedented.
Setting new boundaries
Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."
She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.
Can you make solar power work when the sun goes down? You can, and Dubai is about to run a city that way.
- A new concentrated solar plant is under construction in Dubai.
- When it opens next year, it will be the largest plant of its kind on Earth.
- Concentrated solar power solves the problem of how to store electricity in ways that solar pannels cannot.
Believe it or not, for a few decades, giving people "milk transfusions" was all the rage.
- Prior to the discovery of blood types in 1901, giving people blood transfusions was a risky procedure.
- In order to get around the need to transfuse others with blood, some doctors resorted to using a blood substitute: Milk.
- It went pretty much how you would expect it to.
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