​A hot new tool to edit the human genetic code has a big wow factor: the promise of long-sought cures for intractable diseases. But depending on how it’s used, that same tool could also alter human heredity.

The debate has brought hundreds of scientists and ethicists from 20 countries to a highly unusual, three-day meeting in Washington on the ethics of human gene editing. The meeting concludes Thursday.

“We could be on the cusp of a new era in human history,” Nobel laureate David Baltimore of the California Institute of Technology said Tuesday, in opening the international summit to examine what he called “deep and disturbing questions.”

“The overriding question is when, if ever, would we want to use gene editing to change human inheritance?” Baltimore said.

About the 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:

  1. 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?
  2. What are the potential clinical applications that may hold promise for the treatment of human diseases? What alternative approaches exist?
  3. 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?
  4. 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?
  5. 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?
  6. 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?
  7. 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

That question gained urgency after Chinese researchers made the first attempt at altering genes in human embryos, a laboratory experiment that didn’t work well but did raise the prospect of one day modifying genes in a way that goes far beyond helping one sick person. The process could also pass those alterations on to future generations.

“That really does raise the issue of, how do we use this technology in a responsible fashion,” said molecular biologist Jennifer Doudna of the University of California, Berkeley, who helped pioneer the most-used gene-editing tool. Her calls for debate on its implications and boundaries led to this week’s gathering, a step that could eventually lead to research recommendations.

At issue are tools to precisely edit genes inside living cells, finding specific sections of DNA to slice and repair or replace much like a biological version of cut-and-paste software. There are a few methods but one with the wonky name CRISPR-Cas9 is so fast, cheap and simple for biologists to use that research is booming.

The potential is huge: Scientists are engineering animals with humanlike disorders to unravel the gene defects that fuel them. They’re developing treatments for muscular dystrophy, sickle cell disease, cancer and HIV. They’re trying to grow transplantable human organs inside pigs. They’re even hatching mutant mosquitoes designed to be incapable of spreading malaria, and exploring ways to wipe out invasive species.

One hurdle is safety. While the CRISPR tool is pretty precise, it sometimes cuts the wrong section of DNA. Tuesday, CRISPR pioneer Feng Zhang of the Broad Institute at MIT and Harvard reported tweaking the tool’s molecular scissors to significantly lower chances of off-target editing errors — an improvement that could have implications both for developing therapies and for germline research.

“The reality is, it will be years until this is turned into some kind of a therapy,” Doudna cautioned reporters.

Yet many scientists said it’s not too early to consider the biggest ethical quandary, that performing what’s called germline editing, manipulating reproductive cells — sperm, eggs or embryos — could spread gene changes to future generations.

In the U.S., germline editing for clinical use — meaning for pregnancy — “is a line that should not be crossed at this time,” said John Holdren of the White House Office of Science and Technology Policy.

Last spring’s experiment in China highlighted that, ethics aside, embryo editing wasn’t anywhere near ready for real-world use because those off-target edits risked fixing one problem only to create another.

But there’s controversy over whether and how to continue laboratory experiments to see if it eventually could work. And just as fraudulent stem cell clinics already lure desperate patients, there’s worry about misuse of gene-editing techniques before they’re proven.

Around the world, laws and guidelines vary widely about what germline, or hereditary, research is allowed. Some ban any research; some allow only lab research but not pregnancies; some have no policies. In the U.S., the National Institutes of Health won’t fund germline research but private funding is allowed.

What one country attempts “will have consequences in others,” the White House’s Holdren noted.

It’s not just about editing embryos. At the University of Pittsburgh, Dr. Kyle Orwig is exploring treatments for male infertility that could alter sperm-producing cells that don’t do their job.

Critics note there are other ways to halt transmission of inherited disease. Already, couples undergo in vitro fertilization and have the resulting embryos tested for the family’s problem gene before deciding which to have implanted, noted Marcy Darnovsky of the Center for Genetics and Society advocacy group.

Allowing gene editing for medical reasons would open the door to designer babies with cosmetic changes, too, she added.

“It would alter future human societies, perhaps profoundly so,” Darnovsky said.

Pre-testing of embryos doesn’t solve the problem for all families with devastating rare diseases, said Dr. George Daley of Boston Children’s Hospital, recounting families that have dozens of embryos created through IVF to come up with one or two usable ones.

“Is it more ethical to edit embryos, or to screen a lot of embryos and throw them away? I don’t know the answer,” Doudna said.



Human gene-editing initiative: http://bit.ly/1YDu8OU