Opinion: We need to know what happened to CRISPR twins Lulu and Nana – MIT Technology Review
Posted: December 5, 2019 at 2:49 am
Its been a year since He Jiankui announced that hed made the worlds first gene-edited human babies, twin girls with the pseudonyms Lulu and Nana. Widespread condemnation of his actions followed the announcement. But the facts of the case remain unclear, because he has not been transparent about his work.
In his single public appearance following his announcement, at the Second International Summit on Human Genome Editing in Hong Kong in November 2018, He presented his work by racing through about 60 slides in just 20 minutes. Although he showed data about what he had done to the twins genes, it was blink-and-youll-miss-it, and not enough to convince anyone of his claim that hed safely edited the genomes of the human IVF embryos that became Lulu and Nana.
At the summit, He did say hed just submitted a manuscript describing this work to a scientific journal. Twelve months later, however, the manuscript has remained unpublished and its contents mysterious.
He was asked at the summit why he hadnt posted his manuscript to a preprint server such as bioRxiv or on a public websitesomething scientists frequently do to invite feedback on early drafts. He claimed that hed intended to do so, but colleagues had advised him to allow the manuscript to go through peer review by other scientists before posting it. (Normally, formal peer review takes place only when an academic journal is considering publishing a paper.)
By deciding not to release his manuscript right away, He has made it difficult for other scientists to figure out exactly what he did and how he did it. We already know that there were profound ethical problems with Hes work in germline gene editing, which refers to genetic alterations to embryosor to egg or sperm cellsthat can be passed down through the generations. But its scientific merit, and especially its safety, have remained in question.
When I first had the opportunity to look through a complete manuscript from He last November, I immediately realized there were problems.
The most serious was rampant mosaicism. This means that the gene edits He made to the embryos didnt take effect uniformly: different cells showed different changes. Evidence of mosaicism is present in both Lulus and Nanas embryos, as well as in Lulus placenta, making it likely the twins themselves are mosaic. Some parts of their bodies may contain the specific edits He said he made, other parts may contain other edits he didnt highlight, and yet other parts may contain no edits at all. This would mean that the purported benefit of Hes editing HIV resistancemay not extend to the twins entire bodies, and they could still be fully vulnerable to HIV.
Sign up for The Download your daily dose of what's up in emerging technology
When judging whether the embryos had edits, He took a few cells from the 200 to 300 present in an IVF embryo and analyzed their DNA. But it was the remaining cells went on to multiply to make up the full body. So it is possible that some parts of the twins bodies have edits that He didnt intend to make (off-target edits) and never had a chance to see. Such off-target edits could cause problems such as cancer and heart disease, and could be passed on to Lulus and Nanas future children.
He apparently didnt realize that his own data revealed extensive mosaicism in the embryos, since he made no note of it in the manuscript I saw. Some have wondered if the CRISPR twins were actually a hoax, but to me, the flaws evident in the data make it clear that they werent. Rather, Hes work was a graphic demonstration of attempted gene editing gone awry. Two living human beings, and potentially their descendants too, will bear the consequences.
You shouldnt have to take my word for any of this. You should be able to judge for yourself, or at least hear what other scientists have to say about it.
However, it seems increasingly unlikely that He will be publishing in a peer-reviewed journal. For one thing, I doubt that any respectable journal would seriously consider publishing research with such ethical problems. And even if one did, and sent the manuscript for peer review, He would be in no position to respond to any technical criticisms with further experimental work. He has been under house arrest, and his laboratory was shut down shortly after his announcement about the twins last year.
The only reason to continue keeping Hes work under wraps would be to preserve his ability to publish it someday in a peer-reviewed journal and earn the imprimatur of scientific quality. The community is under no obligation to grant him this privilege. Indeed, it owes him no professional courtesy at all, any more than it would have owed such courtesy to the doctors responsible for the medical experiments in Nazi Germany or the American scientists in charge of the Tuskegee syphilis study.
Rather, in light of the egregious scientific and ethical lapses inherent in Hes cavalier and secretive efforts to make the worlds first gene-edited babies, it is he who owes all of us a full accounting of his actions. Since he has shirked his responsibility to make his work public, its up to others to step in.
Why must the information be public? Its because Hes work reveals serious, unresolved safety concerns. Its not clear that any effort to directly edit human embryos, even if done ethically and with full social approval, can reliably avoid these problems.
International committees convened by the World Health Organization, the US National Academies of Medicine and Sciences, and the Royal Society are currently working to propose regulatory frameworks for doing clinical germline gene editing safely, if it is to be done at all. How can the committees properly do their work without fully understanding all the scientific problems with the single real-world application of clinical germline gene editing thats been attempted to date?
Most worrying is that scientists like Denis Rebrikov in Russia aspire to follow in Hes footsteps. Rebrikov has said hell be able to edit the human germline safely. But how can Rebrikov credibly claim to be able to do better than He if the nature of the problems with Hes work arent widely known? How can the Russian authorities properly evaluate the safety of his proposals without being able to refer to Hes work for guidance?
Its time for the scientific community to fully understand what happened with Lulu and Nana, and to avoid stumbling down a path toward further ill-starred experiments with clinical germline gene editing.
Kiran Musunuru is an associate professor of cardiovascular medicine and genetics at the Perelman School of Medicine at the University of Pennsylvania and the author of The CRISPR Generation, a book about the history of gene editing and the Chinese twins.
See original here:
Opinion: We need to know what happened to CRISPR twins Lulu and Nana - MIT Technology Review
- 'CRISPR pill' instructs harmful bacteria to self-destruct - National Hog Farmer [Last Updated On: April 26th, 2017] [Originally Added On: April 26th, 2017]
- Highly sensitive CRISPR diagnostic tool created - BioNews [Last Updated On: April 26th, 2017] [Originally Added On: April 26th, 2017]
- More Tooth, More Tail in CRISPR Operations | GEN - Genetic Engineering & Biotechnology News (press release) [Last Updated On: April 26th, 2017] [Originally Added On: April 26th, 2017]
- Quick, Sensitive Diagnostic Tests with CRISPR - Technology Networks [Last Updated On: April 26th, 2017] [Originally Added On: April 26th, 2017]
- MPEG LA Invites CRISPR-Cas9 Patents to be Pooled in a One-Stop License - Yahoo Finance [Last Updated On: April 26th, 2017] [Originally Added On: April 26th, 2017]
- What Is CRISPR? - livescience.com [Last Updated On: April 26th, 2017] [Originally Added On: April 26th, 2017]
- CRISPR and Stem Cells Identify Novel Chlamydia Drug Targets - Genetic Engineering & Biotechnology News [Last Updated On: April 26th, 2017] [Originally Added On: April 26th, 2017]
- CRISPR webinar: HGF discusses IP landscape - Life Sciences Intellectual Property Review (subscription) [Last Updated On: April 27th, 2017] [Originally Added On: April 27th, 2017]
- CRISPR.com was for sale, and you won't guess who bought it - STAT [Last Updated On: April 27th, 2017] [Originally Added On: April 27th, 2017]
- CRISPR Pill May Be Key in Fight Against Antibiotic Resistance - Singularity Hub [Last Updated On: April 27th, 2017] [Originally Added On: April 27th, 2017]
- Intellia (NTLA), CRISPR Therapeutics (CRSP) Receive U.S. Patent for CRISPR/Cas9 Ribonucleoprotein Complexes - StreetInsider.com [Last Updated On: April 27th, 2017] [Originally Added On: April 27th, 2017]
- transOMIC technologies Launches transEDIT-dual CRISPR ... - PR Newswire (press release) [Last Updated On: April 27th, 2017] [Originally Added On: April 27th, 2017]
- Global CRISPR Market Forecast 2017-2025 - Research and Markets ... - Business Wire (press release) [Last Updated On: April 27th, 2017] [Originally Added On: April 27th, 2017]
- Quick, Sensitive Diagnostic Tests with CRISPR | Technology Networks - Technology Networks [Last Updated On: April 27th, 2017] [Originally Added On: April 27th, 2017]
- CRISPR/Cas9 and Targeted Genome Editing: A New Era in ... [Last Updated On: April 27th, 2017] [Originally Added On: April 27th, 2017]
- CRISPR - Wikipedia [Last Updated On: April 27th, 2017] [Originally Added On: April 27th, 2017]
- CRISPR Used To Modify Multiple Genes In Rice - Asian Scientist Magazine [Last Updated On: April 28th, 2017] [Originally Added On: April 28th, 2017]
- Current CRISPR Patent Dispute, Explained - CALIFORNIA [Last Updated On: April 28th, 2017] [Originally Added On: April 28th, 2017]
- CEOs of top gene-editing firms got huge compensation hikes last year - Boston Business Journal [Last Updated On: April 28th, 2017] [Originally Added On: April 28th, 2017]
- CRISPR-SMART Cells Regenerate Cartilage, Secrete Anti-Arthritis Drug - Genetic Engineering & Biotechnology News [Last Updated On: April 29th, 2017] [Originally Added On: April 29th, 2017]
- Another CRISPR Trial Begins - GenomeWeb [Last Updated On: April 29th, 2017] [Originally Added On: April 29th, 2017]
- China Is Racing Ahead of the US in the Quest to Cure Cancer With CRISPR - Gizmodo [Last Updated On: April 29th, 2017] [Originally Added On: April 29th, 2017]
- CRISPR Gene Editing - CRISPR/Cas9 - Horizon Discovery [Last Updated On: May 1st, 2017] [Originally Added On: May 1st, 2017]
- CRISPR | Broad Institute [Last Updated On: May 1st, 2017] [Originally Added On: May 1st, 2017]
- Questions and Answers about CRISPR | Broad Institute [Last Updated On: May 1st, 2017] [Originally Added On: May 1st, 2017]
- CRISPR Genome Engineering Resources | learn, share, and discuss [Last Updated On: May 1st, 2017] [Originally Added On: May 1st, 2017]
- CRISPR Technology Scientists on Their Gene Editing Tool - TIME [Last Updated On: May 1st, 2017] [Originally Added On: May 1st, 2017]
- Cas9 - Wikipedia [Last Updated On: May 1st, 2017] [Originally Added On: May 1st, 2017]
- Using CRISPR against cancer shows success in mice - Futurity - Futurity: Research News [Last Updated On: May 2nd, 2017] [Originally Added On: May 2nd, 2017]
- Using CRISPR to Find Treatments for Aggressive Pediatric Brain Cancer - Bioscience Technology [Last Updated On: May 2nd, 2017] [Originally Added On: May 2nd, 2017]
- CRISPR Eliminates HIV in Live Animals - Genetic Engineering & Biotechnology News [Last Updated On: May 2nd, 2017] [Originally Added On: May 2nd, 2017]
- The CRISPR patent dispute - Europe and the US - BioNews [Last Updated On: May 2nd, 2017] [Originally Added On: May 2nd, 2017]
- How Scientists Think CRISPR Will Change Medicine - TIME [Last Updated On: May 3rd, 2017] [Originally Added On: May 3rd, 2017]
- What you need to know about the legal battle over CRISPR patents - Genetic Literacy Project [Last Updated On: May 4th, 2017] [Originally Added On: May 4th, 2017]
- Scientists have eliminated HIV in mice using CRISPR - TechCrunch [Last Updated On: May 4th, 2017] [Originally Added On: May 4th, 2017]
- CRISPR Therapeutics Appoints Samarth Kulkarni, Ph.D. as President, Expanding Role Beyond Chief Business Officer ... - GlobeNewswire (press release) [Last Updated On: May 4th, 2017] [Originally Added On: May 4th, 2017]
- ECDC says risk from contaminated CRISPR kits low - CIDRAP [Last Updated On: May 4th, 2017] [Originally Added On: May 4th, 2017]
- CRISPR Could Transform the Way We Diagnose Disease - Gizmodo [Last Updated On: May 4th, 2017] [Originally Added On: May 4th, 2017]
- A cancer gene also grows stem cells, CRISPR in monkey embryo ... - Speaking of Research [Last Updated On: May 5th, 2017] [Originally Added On: May 5th, 2017]
- New CRISPR Technique Can Potentially Stop Cancer In Its Tracks - Wall Street Pit [Last Updated On: May 6th, 2017] [Originally Added On: May 6th, 2017]
- CRISPR gene-editing tool targets cancer's "command center" - Gizmag - New Atlas [Last Updated On: May 7th, 2017] [Originally Added On: May 7th, 2017]
- Update: CRISPR - Radiolab [Last Updated On: May 7th, 2017] [Originally Added On: May 7th, 2017]
- Cambridge gene editing firm CRISPR to use delivery tech honed ... - Boston Business Journal [Last Updated On: May 9th, 2017] [Originally Added On: May 9th, 2017]
- Oxford Genetics licenses CRISPR tech to power synbio push - FierceBiotech [Last Updated On: May 10th, 2017] [Originally Added On: May 10th, 2017]
- What You Need to Know About the New CRISPR Cancer Treatment - BOSS Magazine [Last Updated On: May 11th, 2017] [Originally Added On: May 11th, 2017]
- CRISPR: The Future of Medicine and Human Evolution - in-Training [Last Updated On: May 12th, 2017] [Originally Added On: May 12th, 2017]
- Intellia Therapeutics Announces Progress with CRISPR/Cas9 at the American Society of Gene & Cell Therapy Annual ... - GlobeNewswire (press... [Last Updated On: May 13th, 2017] [Originally Added On: May 13th, 2017]
- Pac-Man like CRISPR enzymes discovered - Lab News [Last Updated On: May 13th, 2017] [Originally Added On: May 13th, 2017]
- Coming age of CRISPR gene editing: What in heck is the 'Pink Chicken Project'? - Genetic Literacy Project [Last Updated On: May 15th, 2017] [Originally Added On: May 15th, 2017]
- Intellia moves closer to clinic with CRISPR tech - FierceBiotech [Last Updated On: May 15th, 2017] [Originally Added On: May 15th, 2017]
- Will CRISPR Technology Create a New "Human" Species? - Big Think [Last Updated On: May 15th, 2017] [Originally Added On: May 15th, 2017]
- Caribou Bioscience's CEO on CRISPR's legal and ethical challenges - TechCrunch [Last Updated On: May 16th, 2017] [Originally Added On: May 16th, 2017]
- Cut Out the Hype: Gene Editing With CRISPR and the Truth about Superhuman 'Designer Babies' - WhatIsEpigenetics.com (blog) [Last Updated On: May 16th, 2017] [Originally Added On: May 16th, 2017]
- CRISPR-Cas.org [Last Updated On: May 16th, 2017] [Originally Added On: May 16th, 2017]
- Synthego's genetic toolkit aims to make CRISPR more accessible - TechCrunch [Last Updated On: May 16th, 2017] [Originally Added On: May 16th, 2017]
- What is CRISPR? A Beginner's Guide | Digital Trends [Last Updated On: May 16th, 2017] [Originally Added On: May 16th, 2017]
- Geneticists Enlist Engineered Virus and CRISPR to Battle Citrus Disease - Scientific American [Last Updated On: May 16th, 2017] [Originally Added On: May 16th, 2017]
- Editas delays IND for Allergan-partnered CRISPR program - FierceBiotech [Last Updated On: May 16th, 2017] [Originally Added On: May 16th, 2017]
- Easy DNA Editing Will Remake the World. Buckle Up - WIRED [Last Updated On: May 16th, 2017] [Originally Added On: May 16th, 2017]
- Can CRISPR feed the world? - Phys.org - Phys.Org [Last Updated On: May 19th, 2017] [Originally Added On: May 19th, 2017]
- Gene-editing tool 'CRISPR' gaining massive attention - KMOV.com [Last Updated On: May 19th, 2017] [Originally Added On: May 19th, 2017]
- Fixing the tomato: CRISPR edits correct plant-breeding snafu - Nature.com [Last Updated On: May 19th, 2017] [Originally Added On: May 19th, 2017]
- Beyond just promise, CRISPR is delivering in the lab today - The Conversation US [Last Updated On: May 20th, 2017] [Originally Added On: May 20th, 2017]
- What is CRISPR-Cas9, and will it change the world? | Alphr - Alphr [Last Updated On: May 20th, 2017] [Originally Added On: May 20th, 2017]
- Fixing the Tomato: CRISPR Edits Correct Plant-Breeding Snafu ... - Scientific American [Last Updated On: May 20th, 2017] [Originally Added On: May 20th, 2017]
- This UK Biotech uses CRISPR-Cas9 To Fight Bacterial Resistance - Labiotech.eu (blog) [Last Updated On: May 21st, 2017] [Originally Added On: May 21st, 2017]
- Can CRISPR feed the world? | Horizon: the EU Research ... - Horizon magazine [Last Updated On: May 21st, 2017] [Originally Added On: May 21st, 2017]
- Will this gene-editing tool cure the diseases of the future? - Sacramento Bee [Last Updated On: May 23rd, 2017] [Originally Added On: May 23rd, 2017]
- How the CRISPR-Cas9 System is Redefining Drug Discovery - Labiotech.eu (blog) [Last Updated On: May 23rd, 2017] [Originally Added On: May 23rd, 2017]
- Scientists are using gene editing to create the perfect tomato for your salad - Quartz [Last Updated On: May 24th, 2017] [Originally Added On: May 24th, 2017]
- Fine-tuning CRISPR to Create Popular Mouse Models - Technology Networks [Last Updated On: May 25th, 2017] [Originally Added On: May 25th, 2017]
- Scientists Are Using CRISPR To "Program" Living Cells - Futurism - Futurism [Last Updated On: May 25th, 2017] [Originally Added On: May 25th, 2017]
- CRISPR gene editing puts the brakes on cancer cells - Cosmos [Last Updated On: May 26th, 2017] [Originally Added On: May 26th, 2017]
- Watch This Scientist Brilliantly Explain CRISPR to Everyone from a Child to a Ph.D. - Patheos (blog) [Last Updated On: May 27th, 2017] [Originally Added On: May 27th, 2017]
- Using CRISPR gene editing to slow cancer growth | FierceBiotech - FierceBiotech [Last Updated On: May 27th, 2017] [Originally Added On: May 27th, 2017]
- How A Gene Editing Tool Went From Labs To A Middle-School Classroom - NPR [Last Updated On: May 27th, 2017] [Originally Added On: May 27th, 2017]
- In Just a Few Short Years, CRISPR Has Sparked a Research Revolution - Futurism [Last Updated On: May 29th, 2017] [Originally Added On: May 29th, 2017]
- CRISPR Is Taking Over Science, Breaks Out Of Labs And Invades Schools - EconoTimes [Last Updated On: May 30th, 2017] [Originally Added On: May 30th, 2017]
- Gene-editing technique scientists hope will cure cancer and all ... - The Independent [Last Updated On: May 30th, 2017] [Originally Added On: May 30th, 2017]
- CRISPR Gene-Editing Can Cause Hundreds of Unexpected ... - ScienceAlert [Last Updated On: May 30th, 2017] [Originally Added On: May 30th, 2017]