• Written by Dimitri Perrin, Senior Lecturer, Queensland University of Technology
The team used CRISPR on human embryos in a bid to render them resistant to HIV infection. But instead, they generated different mutations, about which we know nothing. SHUTTERSTOCK

More than a year ago, the world was shocked by Chinese biophysicist He Jiankui’s attempt to use CRISPR technology to modify human embryos and make them resistant to HIV, which led to the birth of twins Lulu and Nana.

Now, crucial details have been revealed in a recent release of excerpts from the study, which have triggered a series of concerns about how Lulu and Nana’s genome was modified.

How CRISPR works

CRISPR is a technique that allows scientists to make precise edits to any DNA by altering its sequence.

When using CRISPR, you may be trying to “knock out” a gene by rendering it inactive, or trying to achieve specific modifications, such as introducing or removing a desired piece of DNA.


Read more: What is CRISPR gene editing, and how does it work?


Gene editing with the CRISPR system relies on an association of two proteins. One of the proteins, called Cas9, is responsible for “cutting” the DNA. The other protein is a short RNA (ribonucleic acid) molecule which works as a “guide” that brings Cas9 to the position where it is supposed to cut.

The system also needs help from the cells being edited. DNA damage is frequent, so cells regularly have to repair the DNA lesions. The associated repair mechanisms are what introduce the deletions, insertions or modifications when performing gene editing.

How the genomes of Lulu and Nana were modified

Jiankui and his colleagues were targeting a gene called CCR5, which is necessary for the HIV virus to enter into white blood cells (lymphocytes) and infect our body.

One variant of CCR5, called CCR5 Δ32, is missing a particular string of 32 “letters” of DNA code. This variant naturally occurs in the human population, and results in a high level of resistance to the most common type of HIV virus.

Jankui’s team wanted to recreate this mutation using CRISPR on human embryos, in a bid to render them resistant to HIV infection. But this did not go as planned, and there are several ways they may have failed.

First, despite claiming in the abstract of their unpublished article that they reproduced the human CCR5 mutation, in reality the team tried to modify CCR5 close to the Δ32 mutation.

As a result, they generated different mutations, of which the effects are unknown. It may or may not confer HIV resistance, and may or may not have other consequences.

Worryingly, they did not test any of this, and went ahead with implanting the embryos. This is unjustifiable.

The mosaic effect

A second source of errors could have been that the editing was not perfectly efficient. This means that not all cells in the embryos were necessarily edited.

When an organism has a mixture of edited and unedited cells, it is called a “mosaic”. While the available data are still limited, it seems that both Lulu and Nana are mosaic.

This makes it even less likely that the gene-edited babies would be resistant to HIV infection. The risk of mosaicism should have been another reason not to implant the embryos.


Read more: 'Designer' babies won't be common anytime soon – despite recent CRISPR twins


Moreover, editing can have unintended impacts elsewhere in the genome.

When designing a CRISPR experiment, you choose the “guide” RNA so that its sequence is unique to the gene you are targeting. However, “off-target” cuts can still happen elsewhere in the genome, at places that have a similar sequence.

Jiankui and his team tested cells from the edited embryos, and reported only one off-target modification. However, that testing required sampling the cells, which were therefore no longer part of the embryos - which continued developing.

Thus, the remaining cells in the embryos had not been tested, and may have had different off-target modifications.

This is not the team’s fault, as there will always be limitations in detecting off-target and mosaicism, and we can only get a partial picture.

However, that partial picture should have made them pause.

A bad idea to begin

Above, we have described several risks associated with the modifications made on the embryos, which could be passed on to future generations.

Embryo editing is only ethically justifiable in cases where the benefits clearly outweigh the risks.

Technical issues aside, Jiankui’s team did not even address an unmet medical need.

While the twins’ father was HIV-positive, there is already a well-established way to prevent an HIV-positive father from infecting embryos. This “sperm washing” method was actually used by the team.

The only benefit of the attempted gene modification, if proven, would have been a reduced risk of HIV infection for the twins later in life.

But there are safer existing ways to control the risk of infection, such as condoms and mandatory testing of blood donations.

Implications for gene editing as a field

Gene editing has endless applications. It can be used to make plants such as the Cavendish banana more resistant to devastating diseases. It can play an important role in the adaptation to climate change.

In health, we are already seeing promising results with the editing of somatic cells (that is, non-heritable modifications of the patient’s own cells) in beta thalassemia and sickle cell disease.

However, we are just not ready for human embryo editing. Our techniques are not mature enough, and no case has been made for a widespread need that other techniques, such as preimplantation genetic testing, could not address.


Read more: Experts call for halt to CRISPR editing that allows gene changes to pass on to children


There is also much work still needed on governance. There have been individual calls for a moratorium on embryo editing, and expert panels from the World Health Organisation to UNESCO.

Yet, no consensus has emerged.

It is important these discussions move in unison to a second phase, where other stakeholders, such as patient groups, are more broadly consulted (and informed). Engagement with the public is also crucial.

Dimitri Perrin has received funding from the Australian Research Council (ARC), the Australian-French Association for Innovation and Research (AFRAN), and the Advance Queensland programme.

Gaetan Burgio receives funding from the National Health and Medical Research Council (NHMRC), the Australian Research Council (ARC), the National Collaborative Research Infrastructure Strategy (NCRIS) via the Australian Phenomics Network (APN) ,Universities Australia and the Natural Science Foundation in China (NSFC).

Authors: Dimitri Perrin, Senior Lecturer, Queensland University of Technology

Read more http://theconversation.com/chinas-failed-gene-edited-baby-experiment-proves-were-not-ready-for-human-embryo-modification-128454

Yes, this continent was invaded in 1788 – an international law expert explains

Should we remember January 26 1788 as “Invasion Day”? The colonisation of Australia was an invasion from an Aboriginal and Torres Strait Islander perspective. But critics of the name &ld...

Rowan Nicholson, Associate Lecturer and Co-director of the Sydney Centre for International Law, University of Sydney - avatar Rowan Nicholson, Associate Lecturer and Co-director of the Sydney Centre for International Law, University of Sydney

29,000 cancers overdiagnosed in Australia in a single year

Men are 17% more likely to be diagnosed with cancer than they were 30 years ago. fizkes/ShutterstockAlmost one in four cancers detected in men were overdiagnosed in 2012, according to our new research...

Alexandra Barratt, Professor of Public Health, University of Sydney - avatar Alexandra Barratt, Professor of Public Health, University of Sydney

How a year of trying to buy nothing made me a smarter shopper and a better teacher

Year 7 students at the International School of Helsinki, Finland, doing a sustainable development exercise with the author (top left) and fellow teacher Rachael Thrash. Katja Lehtonen, Author provided...

Ellen Heyting, PhD student in Education and Head of Years 11 and 12, Monash University - avatar Ellen Heyting, PhD student in Education and Head of Years 11 and 12, Monash University

10½ commandments of writing

Things to keep in mind for writers young and old. Kenny Luo/UnsplashEvery author is asked by new writers for advice. There is, however, no all-encompassing, single answer that also happens to be corre...

Sean Williams, Lecturer, Flinders University - avatar Sean Williams, Lecturer, Flinders University

How smart were our ancestors? Turns out the answer isn't in brain size, but blood flow

Skulls hold clues to intelligence. (Clockwise from left: Australopithecus, orangutan, gorilla, chimpanzee) Roger Seymour, Author providedHow did human intelligence evolve? Anthropologists have studied...

Roger S. Seymour, Professor Emeritus of Physiology, University of Adelaide - avatar Roger S. Seymour, Professor Emeritus of Physiology, University of Adelaide

The Wuhan coronavirus is now in Australia – here's what you need to know

New South Wales Health has confirmed three men in their 30s, 40s and 50s in Sydney have tested positive to the new Wuhan coronavirus after returning from China. This follows Australia’s first c...

Sanjaya Senanayake, Associate Professor of Medicine, Infectious Diseases Physician, Australian National University - avatar Sanjaya Senanayake, Associate Professor of Medicine, Infectious Diseases Physician, Australian National University

The best recipes for gin drink from around the world

Gin is a very interesting drink to explore. Gin is a surprisingly versatile drink when it comes to the flavor profile and can have different ranges of flavor profile when trying out different brands...

News Company - avatar News Company

The Most In-Demand Jobs for 2020

When choosing their career, a lot of people focus exclusively on the paycheck; however, this is definitely not all that matters. Whether or not a profession is in-demand will certainly affect the ...

Diana Smith - avatar Diana Smith

4 Ways Art and Creativity Raises Satisfied Children

Sydney is more than the Opera House, countless bars, and the harbour. Around it is the many suburbs that are excellent places to raise a family. From Hunters Hill to Gladesville, these areas offer...

News Company - avatar News Company

Sick and Tired of Your Dead End Job? Try Teaching!

Tired of the same old grind at the office? Want an opportunity to impact lives both in your community and around the world? Do you love to travel and have new experiences? Teaching English is the perfect job for you! All you need is a willingness to ...

News Company - avatar News Company

The Impact of an Aging Population in Australia

There’s an issue on the horizon that Australia needs to prepare for. The portion of elderly citizens that make up the country’s overall population is increasing, and we might not have the infrastructure in place to support this. Australians h...

News Company - avatar News Company