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July 2, 2019 - July 8, 2020
Cancer
eliminating these mutations before they have a chance to do irreversible harm.
expanding our understanding of cancer biology, and it is also accelerating immunotherapy treatments, which harness the body’s own immune system to fight cancer.
The critical cancer-causing mutations are buried in a vast sea of auxiliary mutations that don’t directly affect disease pathology. In fact, one of the hallmarks of cancer is the increased rate at which DNA mutations creep into the genome, making it difficult to identify the mutations that are actually playing the largest role in causing tumors.
Unlike the gene-editing technologies that preceded CRISPR, the process of designing CRISPR to home in on a new twenty-letter sequence in the genome is simple enough for a high school student to master—so simple, indeed, that a computer can be programmed to do it.
But instead of asking what gene mutations caused the cancer (as Ebert’s team had done), Sabatini’s team wanted to discover gene mutations that disabled the cancer.
By identifying new genetic susceptibilities of leukemias and lymphomas, these experiments revealed promising new targets for chemotherapy drugs. Subsequent experiments by other laboratories have revealed the weak spots of other types of cancer, among them colorectal cancer, cervical cancer, melanoma, ovarian cancer, and glioblastoma
distinguish one individual’s cancer from another and that will offer hints of how to tailor treatments to match the specific biology of each particular disease.
immunotherapy.
where a single batch of engineered T cells, designed for a specific type of cancer, could be given universally to all patients suffering from that pathology.
Layla was a one-year-old
we’ll have to solve one major problem with gene editing.
CRISPR could make occasional mistakes and confuse one letter of DNA for another.
To be sure, virtually all medical drugs have some kind of off-target activity, and as long as the intended on-target benefits outweigh those risks, physicians and regulators are generally pretty forgiving. For instance, antibiotics kill off both pathogenic bacterial strains and beneficial strains, and chemotherapy drugs kill off both cancerous cells and healthy cells. The challenge is ultimately one of specificity: developing a drug that is so closely matched to its intended target that a few atoms out of place will weaken the interaction enough to prevent the drug from causing unintended
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the side effects of a medication typically cease once a patient stops taking the drug. With gene editing, however, any off-target DNA sequence, once edited, is irreversibly changed. Not only will unintended edits to the DNA be permanent, they will also be copied into every cell that descends from the first one. And although most random edits are unlikely to damage the cell, if we’ve learned anything from certain diseases and cancers, it’s that even a single mutation can be enough to wreak havoc on an organism.
computer algorithms that will automatically probe the three-billion-letter human genome to see how many other regions have sequences similar to the one a scientist wants to edit.
Before ever selecting a DNA sequence to edit in patients, scientists will exhaustively test a bunch of related DNA sequences in cultured cells, determine which ones have the least number of off-target effects, and only then—once they have the winner—will they proceed to clinical trials.
third strategy
engineering CRISPR to be more discriminating in how it recognizes the target DNA.
Finally, the dosage of CRISPR affects the likelihood of the genome being riddled with unintended mutations.
growing list of diseases for which potential genetic cures have been developed with CRISPR: achondroplasia (dwarfism), chronic granulomatous disease, Alzheimer’s disease, congenital hearing loss, amyotrophic lateral sclerosis (ALS), high cholesterol, diabetes, Tay-Sachs, skin disorders, fragile X syndrome, and even infertility.
I think we should refrain from using CRISPR technology to permanently alter the genomes of future generations of human beings,
I found myself lying awake in the wee hours of the night wondering about people outside of academia who were also taking a keen interest in this burgeoning field, and not always for the best reasons.
she hoped to offer some lucky couple the first healthy “CRISPR baby.” The child, she explained, would be produced in the lab using in
customized DNA mutations, installed via CRISPR, to eliminate any possibility of genetic disease.
I was especially beginning to worry if, someday soon, scientists would attempt to alter the human genome in a heritable way, not to treat a disease in a living patient, but to eliminate the prospect of disease in a child who hadn’t yet been born or even conceived. This was, after all, exactly what Christina had proposed to Sam.
potential to turn not only living people’s genomes but also all future genomes into a collective palimpsest upon which any bit of genetic code could be erased and overwritten depending on the whims of the generation doing the editing.
not everyone shared my trepidation about the prospect of scientists rewriting the DNA of future human beings without fully appreciating the consequences.
it might well change the course of our species’ history in the long run, in ways that were impossible to foretell.
Marshall Nirenberg,
“Decisions concerning the application of this knowledge must ultimately be made by society, and only an informed society can make such decisions wisely.”
Robert Sinsheimer,
“potentially one of the most important concepts to arise in the history of mankind . . . For the first time in all time a living creature understands its origin and can undertake to design its future.”
French Anderson,
“might be like the young boy who loves to take things apart.
Louise Brown in 1978, the world’s first “test-tube baby,”
first successful cloning of a mammal with the famous birth of Dolly the sheep in 1996.
IVF and cloning were huge technical breakthroughs that helped lay the groundwork for germline modification. Not only did they show that scientists could generate a viable embryo in the lab by mixing egg and sperm, they also revealed that the embryos could be created using genetic information from a single animal.
Once we fully understood the genetic factors that determine human health and performance, we might be able to select for—or perhaps even engineer—embryos with a genetic composition different than that of their parents. Better than that of their parents.
the first symposia on the topic at the University of California, Los Angeles. Called Engineering the Human Germline,
these researchers grappled with the thorny question of whether scientists would be transgressing natural or divine laws by changing the human germline and whether such efforts would constitute eugenics, a fallacious early-twentieth-century set of beliefs and practices that have since been thoroughly repudiated by mainstream science.
Panel discussions focused on topics such as eradicating disease, avoiding serious genetic defects, and generally improving on the natural course of evolution—which, attendees argued, could be so cruel as to justify some sort of intervention.
Instead of implanting random embryos into the mother, IVF doctors could first analyze the DNA of candidate embryos to make sure they were selecting ones with the healthiest
its earliest implementations, PGD was used for gender selection, albeit for medical reasons;
the use of preimplantation genetic diagnosis for gender selection is illegal in many countries (including India and China) or permitted only to avoid X-linked diseases (as in Great Britain). But it’s legal in the United States,
birth of so-called savior siblings, destined from the moment of implantation not only to live their own lives, but also to serve as organ or cell donors for a sibling.
what’s to stop fertility clinics from consulting this genetic information so they can offer their consumers even more choices when it comes to selecting the most desirable or “best” embryos?
The second egg cell contains no nucleus but does have mitochondria, which house a small portion of the human genome,
three-parent IVF would permanently alter the human genome, changing the germline in ways that
would be passed on to future generations in perpetuity. Regulators have nevertheless greenlighted this reproductive therapy.
