Britain’s decision to allow researchers to edit the genes of human embryos — not to create babies but to start unraveling the earliest stages of development — is raising new questions about the ethics of this hot new technology.

Genome editing is a technique that lets scientists alter the DNA of plants, animals or humans more precisely than ever before, much like a biological cut-and-paste program. Scientists say one day the technique might help treat devastating inherited diseases, such as muscular dystrophy, or wipe out malaria-carrying mosquitoes.

But one concern is that gene editing also might eventually lead to so-called designer babies.

Last summer, researchers from North Carolina State University and the University of North Carolina at Chapel Hill for the first time created and used a nanoscale vehicle made of DNA to deliver{[/a}} a CRISPR-Cas9 gene-editing tool into cells in both cell culture and an animal model.

The CRISPR-Cas system, which is found in bacteria and archaea, protects bacteria from invaders such as viruses. It does this by creating small strands of RNA called CRISPR RNAs, which match DNA sequences specific to a given invader. When those CRISPR RNAs find a match, they unleash Cas9 proteins that cut the DNA. In recent years, the CRISPR-Cas system has garnered a great deal of attention in the research community for its potential use as a gene editing tool – with the CRISPR RNA identifying the targeted portion of the relevant DNA, and the Cas protein cleaving.

And in December, a task force from the National Academies of Science, Engineering and Medicine launched a study into the ethics of gene editing. (Details below). A conference of scientists in Washington, D.C. warned against designer babies but supported research.

Here’s a look at the science and controversy as provided by the Associated Press:

WHAT IS GENE EDITING

While scientists have long been able to find defective genes, fixing them has been so cumbersome that it’s slowed development of genetic therapies. With gene editing, scientists home in on a piece of DNA and use molecular tools that act as scissors to snip that spot — deleting a defective gene, repairing it or replacing it.

There are some older methods but a new tool called CRISPR-Cas9 has been adopted by laboratories worldwide because it’s faster, cheaper, simple enough to use with minimal training and allows altering of multiple genes simultaneously.

WHAT IT MIGHT TREAT

The biggest use so far is to rapidly engineer animals with human-like disorders for basic research, but promising gene-editing experiments make regular headlines.

Much like a bone marrow transplant, researchers hope to use CRISPR for diseases like sickle cell, correcting the faulty gene in someone’s own blood-producing cells rather than implanting donated ones.

Similarly, doctors in Britain recently treated a 1-year-old with leukemia using donated immune cells that had been experimentally altered with an older editing method to target her cancer. A California company is testing a non-CRISPR way to make HIV patients’ immune cells better resist the virus.

The University of Massachusetts just reported using a CRISPR technique to switch off, rather than cut and repair, a gene in muscle cells that causes one form of muscular dystrophy.

And Harvard researchers recently edited 62 spots in pig DNA, part of work to use the animals to grow organs for human transplant.

THE BIGGEST HURDLE

Safety is a key question because gene editing isn’t always precise enough; there’s the possibility of accidentally cutting DNA that’s similar to the real target. Out-of-body treatments like altering blood cells get around the fear of fixing one problem only to spark another, and efforts to improve precision are underway.

THE ETHICS CONTROVERSY

Altering genes in sperm, eggs or embryos can spread those changes to future generations, so-called germline engineering that might one day stop parents from passing inherited diseases to their children.

Chinese scientists reported the first-known attempt to edit human embryos last spring, working with leftovers from fertility clinics that never could have developed into fetuses. They aimed to correct a deadly inherited gene, but uncovered problems that will require more research.

Among the ethical concerns are that future generations couldn’t consent, and any long-term negative effects might not become apparent for years. There’s also concern about babies designed for better intellect, athleticism or appearance rather than to prevent disease.

In December, international scientists and ethicists gathered at the U.S. National Academy of Sciences declared that while gene-editing is nowhere near ready to use for pregnancy, altering early embryos as part of careful laboratory research should be allowed even as society grapples with the ethical questions.

And on Monday, Britain’s Human Fertilisation and Embryology Authority announced it was granting permission for that kind of laboratory research at the Francis Crick Institute, a study of the genes human embryos need to develop properly in the first seven days.

IS IT LEGAL

Where you live determines if, or what kind of, research can be performed on embryos. Some countries, especially in Europe, ban germline research. Others, such as China, have guidelines described as unenforceable. Britain allows basic lab research only.

In the U.S., the NIH won’t fund research involving germline editing but private funding is allowed.

BEYOND MEDICINE

Human gene editing aside, there are environmental concerns, too. Experiments are underway to force genetic changes to spread rapidly through populations of animals and plants — changes that could wipe out invasive species or disease-carrying insects. A California team recently reported a first step, hatching malaria-resistant mosquitoes that could easily spread their new protective gene to their offspring.


About the Gene Editing Study

Background

Gene-editing technologies hold great promise for advancing science and improving human health. Powerful new tools, such as CRISPR-Cas9, allow researchers with basic knowledge of molecular biology to precisely modify the genetic makeup of any living organism. The possible applications for such technologies are many. In humans, the technologies could offer a cure to often devastating genetic diseases such as Huntington’s disease and sickle cell anemia, and help improve understanding and treatment of many other illnesses.

However, these new avenues of research also present many complex challenges, both to the scientific and medical communities and to society as a whole. The availability of new technologies has intensified debate among scientists and physicians about such research. We are at a critical juncture in genetic research.  What is needed now is guidance that is based on an in-depth review of the science underlying gene editing and an understanding of the potential benefits as well as the valid concerns raised by this research.

Statement of Task

The study will examine the scientific underpinnings as well as the clinical, ethical, legal, and social implications of the use of human genome editing technologies in biomedical research and medicine.  It will address the following issues related to human gene editing, including editing of the human germline:

  • What is the current state of the science of human gene editing, as well as possible future directions and challenges to further advances in this research?
  • What are the potential clinical applications that may hold promise for the treatment of human diseases? What alternative approaches exist?
  • What is known about the efficacy and risks of gene editing in humans, and what research might increase the specificity and efficacy of human gene editing while reducing risks? Will further advances in gene editing introduce additional potential clinical applications while reducing concerns about patient safety?
  • Can or should explicit scientific standards be established for quantifying off-target genome alterations and, if so, how should such standards be applied for use in the treatment of human diseases?
  • Do current ethical and legal standards for human subjects research adequately address human gene editing, including germline editing? What are the ethical, legal, and social implications of the use of current and projected gene-editing technologies in humans?
  • What principles or frameworks might provide appropriate oversight for somatic and germline editing in humans? How might they help determine whether, and which applications of, gene editing in humans should or should not go forward? What safeguards should be in place to ensure proper conduct of gene-editing research and use of gene-editing techniques?
  • Provide examples of how these issues are being addressed in the international context. What are the prospects for harmonizing policies? What can be learned from the approaches being applied in different jurisdictions?

The committee will address these questions and prepare a report that contains its findings and recommendations. The report will provide a framework based on fundamental, underlying principles that may be adapted and adopted by any nation that is considering the development of guidelines. The report will also include a focus on advice for the United States.

Source: National Academies of Science, Engineering, Medicine