HONG KONG — He Jiankui, a now-former researcher at Southern University of Science and Technology in Shenzhen, China, rose from obscurity to international scrutiny after revealing to the world that he used a new genetic-editing technique to design two HIV-resistant Chinese baby girls as embryos and implanted them into their mother through in vitro fertilization (IVF).

“Two Chinese girls, called Lulu and Nana, came crying into this world as healthy as any other babies,” He said in a Nov. 25 YouTube video.

The international scientific and medical community responded with shock at He’s claims, which he presented again Nov. 27 at the second International Human Genome Editing Summit in Hong Kong. His claims so far have not been substantiated. But many in China’s scientific community, which has been on the long march to pioneer genetic therapies, swiftly condemned He for using the CRISPR/cas9 editing technique on human embryos.

Many scientists and ethicists, meanwhile, have been quick to point out that CRISPR and other gene-editing technologies have a vast potential to treat even the rarest and most obscure diseases in human beings without moral objections or tampering with humanity’s gene pool. Many of these promising therapies are already under development.

Gene editing is aimed at two different kinds of cells in the body: somatic cells (an individual’s cells) and germ cells (sperm or egg).

 

Hopeful Progress

Janet Lambert, CEO of the Alliance for Regenerative Medicine, which represents more than 300 companies and nonprofits worldwide developing new genetic therapies, told the Register that the vast majority of gene-editing research involves somatic cells. Technology like CRISPR, she indicated, has made it possible to treat a host of diseases that drug companies ordinarily would not touch due to prohibitive expenses and a small market. Lambert explained there are more than 7,000 rare genetic diseases and only a few hundred treatments available. Such diseases include Parkinson’s disease, Type 1 diabetes, sickle cell anemia, Gaucher disease and glioblastoma, among many others.

“The promise of the technology is extraordinary,” Lambert said. Scientists may eventually develop ways to introduce somatic cell therapies into the womb that could save unborn children from fatal diseases, but Lambert said those breakthroughs are a long ways off.

However, editing the human germline poses far greater risks because it introduces a permanent genetic change that can be passed down. Therapeutic human germline editing is not currently permitted in the United States, Lambert explained. Other than rogue scientists like He, she added, scientific research into editing the human germline for therapeutic purposes is not taking place “as far as we know.”

Lambert said both somatic and germline editing could be abused for nontherapeutic purposes. But somatic cell editing “limits the consequences of what you’re doing” to a single person, not the entire human family.

“There’s a need to have a much clearer understanding of the safety and efficacy profile of gene editing in human beings before it starts affecting multiple generations,” she said.

 

What is CRISPR?

Scientists are still at the early stages of understanding CRISPR as a gene-editing tool, explained Kevin Doxzen, science communications specialist at the Innovative Genomics Institute.

CRISPR acts as a “programmable molecular scissors” on the human genome, which has approximately 3 billion base pairs. A genome is an organism’s complete set of deoxyribonucleic acid (DNA), which contains all of the organism’s genetic code.

Doxzen explained that sickle-cell anemia is the result of one letter change on human DNA. But with CRISPR, one can cut out that single-letter base pair. The next step then involves using the body’s natural repair pathways to replace it with other genetic material.

“That next step can be pretty hard,” he said. Some scientists are using CRISPR to modify the mosquitoes most responsible for transmitting malaria, a disease that is devastating populations in Africa.

“The range of CRISPR to treat human diseases is enormous,” he told the Register.

But Doxzen said scientists still have a lot to learn about DNA and how to use CRISPR to cut DNA correctly and avoid the risk of “off-target cutting” of the human genome.

He said that when it comes to germline editing, current technology does not permit germline edits in adults, so the only option would be to do it in embryos. But the biology of the embryo is “very, very poorly understood.”

Doxzen added that He’s experimental data on the CRISPR twin girls is sloppy, but if the gene editing actually occurred, there will be permanent ramifications.

“Essentially He passed down sloppy experiments to future generations,” he said.

 

Moral Considerations

The application of genetic modification technologies on human embryos poses different moral questions than somatic cell gene-editing therapies applied to unborn children in the womb, or adults, explained Father Tadeusz Pacholczyk, a Catholic priest, neuroscientist and director of education at the National Catholic Bioethics Center in Philadelphia.

Father Pacholczyk said mitochondrial gene editing on a human baby would not pose “fundamental moral concerns as long as the risks to the patient from the treatment were low.”

“Sickle-cell anemia would be an example of a disease that is likely to be able to be treated in many adults via gene-therapy approaches,” he added.

But germ-editing human embryos faces multiple moral barriers. The Catholic Church’s viewpoint, Father Pacholczyk explained, grounded in the dignity of the human person, rules out, first of all, creating human embryos in laboratories. The IVF process (involved in embryonic germline editing) violates their human dignity by turning them into objects that are created (or then frozen to be later thawed out).

“Humans deserve to be brought into the world not in the cold, impersonal world of laboratory glassware, but exclusively in the loving, bodily embrace of their parents,” he said.

Unlike the somatic cell gene therapies that could “involve treating the embryo as a unique patient, within his or her mother’s womb,” the germ-line editing of human embryos turns those human beings into “raw laboratory material, prepped up for experimental protocols” that end up being treated as products, subjected to genetic experiments, with the view that “a few of them might end up surviving and developing without the disease.”

“The use of genetic-modification technologies on embryos imposes significant risk for the embryo, simply in terms of the mechanical procedures themselves, the numerous manipulative steps involved, and the risks of potential ‘off-target’ genetic changes that might reasonably be expected to occur,” Father Pacholczyk said.

The priest said encouraging research into genetically modified embryos would “open up the floodgates” for embryos to be created and destroyed in laboratory experiments.

 

Unintended Consequences

And Father Pacholczyk said making edits to embryonic children may involve risks that are only understood when they grow older. The priest pointed out that the changes He made to confer immunity to HIV infection may increase the twins’ susceptibility to West Nile virus and other diseases.

“Is it ever proper to experiment on our own offspring?” he said. “Even when we think we understand the role of a specific gene, we sometimes discover later that it has several functions, and tinkering with it ends up having other surprising downstream effects.”

But these modifications will also be passed into the human gene pool, “establishing permanent and irrevocable changes to our own humanity.”

He asked: “How does one adequately evaluate the risks of such changes?”

 

Peter Jesserer Smith is a Register staff writer.