Second International Summit on Human Genome Editing: Continuing the Global Discussion: Proceedings of a Workshop in Brief

The Policy

Synopsis

The Second International Summit on Human Genome Editing was a meeting between the United States (US) National Academy of Sciences, the US National Academy of Medicine, the Royal Society of the United Kingdom, and the Academy of Sciences of Hong Kong from November 27-29, 2018 in Hong Kong. The meeting included discussions about human genome editing and its implications for human health, ethics, and policy. A subsequent report summarizes the discussions and presentations from the meeting, and features a concluding statement from the meeting’s organizing committee.

A major focus of the meeting was an announcement that Chinese researcher Dr. Jiankui He claimed to have edited the genomes of two twin embryos, leading to the birth of twin girls with a genetic mutation in the CCR5 gene such that they are resistant to the Human Immunodeficiency Virus (HIV). Participants at the meeting expressed concerns about the fact that alternative preventative measures already exist for HIV, the fact that the genetic changes will be transmitted to future generations, and the potential risk for health problems as a result of the genome editing. The summit organizing committee called for Dr. He’s work to be verified by an independent assessment.

Other discussions at the summit highlighted continued research in human genome editing, with a focus on the molecular machinery that interacts with DNA and the need to increase the specificity with which particular sites on DNA can be edited. Cultural and religious perspectives about the ethics of genetically modifying human embryos were also discussed, as well as potential government regulation, such as a global ethical code of values with international collaboration. Finally, attendees discussed how to communicate with the public about human genome editing.

In a statement released after the conference, the organizing committee concluded that further research is needed before heritable genome editing can be conducted responsibly in humans.

Context

The First International Summit on Human Gene Editing was held from December 1-3, 2015 in Washington, DC. Discussions at the first summit recognized a need for continued research on genome editing and its clinical effects, especially in cases where genetic modifications could be passed on to future generations. The Second International Summit on Human Genome Editing (November 27-29, 2018) continued the discussions raised at the first summit, with a particular focus on modifications that can be passed on to offspring.

Just before the second summit (November 25, 2018), information was leaked indicating that a Chinese research team led by Dr. Jiankui He at the Southern University of Science and Technology claimed to have edited the DNA of two human embryos, leading to the birth of twin infants with a mutation in the CCR5 gene that left them resistant to HIV. This information initiated widespread discussion and became a major focus of the second summit.

CRISPR-Cas9 genome editing, developed in 2012, is a technique that enables somatic cells (general cells in the body) to be edited. This technique can contribute to gene therapy, in which genes are edited to prevent or treat a disease. Dr. He’s work, announced in 2018, is different from previous forms of gene editing because it changed the germline (cells which influence the DNA of subsequent generations). In the United States, research on human germline editing is not funded by the National Institutes of Health.

In December 2018, the World Health Organization established an advisory committee to review the scientific, legal, and ethical considerations of genome editing, and to discuss potential government actions to establish global regulations. The committee met for the first time in March 2019.

The Science

Science Synopsis

Genome editing is the process of using specialized cell machinery to edit DNA. DNA is a chemical code consisting of pieces called genes, which provide instructions for the body to carry out internal processes that sustain life and can determine traits such as appearance and health. All of the DNA in a body is collectively known as the genome. By editing the code in DNA, human genome editing could lead to advances in preventing and treating diseases such as blood disorders, immunodeficiency disorders, and Duchenne muscular dystrophy.

Genes can be edited at the level of cells which are not passed on to future generations (somatic cell genome editing), or at the level of cells which influence the next generation (germline editing). At the summit, Dr. He Jiankui announced that he had edited the genome of two embryos to disable the gene CCR5, which normally enables the human immunodeficiency virus (HIV) to infect host cells, making twin girls essentially resistant to the virus. Because these genomes were edited at the embryonic stage, the changes will be preserved in future generations.

Scientific Assumptions

  • Human embryos can be genetically altered, implanted, and later born (“Announcement of Heritable Genome Editing,” Paragraph 1): While it has been established that an embryo can be implanted to induce pregnancy using in vitro fertilization, Dr. He’s announcement is the first known indication of success using a genetically modified human embryo.
  • Genes such as CCR5 can be disabled in vitro, and this procedure is safe for use on human embryos (“Announcement of Heritable Genome Editing,” Paragraph 3): It is well established that genes can be disabled or otherwise modified through common laboratory techniques. However, Dr. He’s claim that the procedure is safe for use on human embryos is not supported by any current studies. The potential risks of such a procedure remain unknown.

The Debate

Scientific Controversies / Uncertainties

The ethics and potential implications of human genome editing are widely debated in the scientific community. While genetically modified animals are common in biomedical research, and genetically modified foods have become more commonplace in recent years, technologies to edit the human genome are less developed, and their potential risks are not fully understood. The general consensus in the scientific community is that further research is needed to determine whether current genome editing techniques are safe to use in humans.

Possible benefits of human genome editing include more effective disease treatment and prevention. For diseases with a pure genetic cause, human genome editing could allow these diseases to be prevented and, if transmitted to future generations, eliminated from the population. Furthermore, genome editing could increase the success rate of in vitro fertilization.

Nevertheless, some scientists are hesitant to support human genome editing technologies. Genetic modifications may lead to adverse health effects or other risks that are currently unknown. The genetic modification performed by Dr. He was especially controversial because treatments and preventions already exist for HIV, raising questions about whether it was worth exposing the infants to unknown risks by modifying the genome.

In addition, ethical concerns have arisen regarding what types of traits should be modified in humans. While genome editing technologies could be used to treat diseases, they could also be used to change other traits such as appearances and cognitive abilities. These possibilities raise questions about whether it is ethical to change such traits, and how tightly the use of these technologies should be regulated by the government or other entities.

Endorsements & Opposition

  • Genetics Society of China and Chinese Society for Stem Cell Research, statement, November 27, 2018: “We strongly condemn [the research led by He] for the extreme irresponsibility, both scientifically and ethically.”
  • Joyce Harper (Professor in Human Genetics and Embryology, University College London), statement, Nature, November 26, 2018: “Today’s report of genome editing human embryos for resistance to HIV is premature, dangerous and irresponsible.”
  • Julian Savulescu (director of the Oxford Uehiro Centre for Practical Ethics, University of Oxford), statement, Nature, November 26, 2018: “This experiment exposes healthy normal children to risks of gene editing for no real necessary benefit.”
  • Fyodor Urnov (genome editing scientist, Altius Institute for Biomedical Sciences), statement, Massachusetts Institute of Technology (MIT) Technology Review, November 25, 2018: “The data I reviewed are consistent with the fact that the editing has, in fact, taken place.… There is, at present, no unmet medical need that embryo editing addresses.”

Potential Impacts

The discussions from the summit may inform future regulations on genome editing research and clinical use, particularly in cases of germline editing where the changes will be transmitted to future generations. Ethicists in China have published a recommendation for Chinese regulations on biomedical research to be reexamined in response to Dr. He’s work. They recommend increased collaboration between researchers and bioethicists, stricter oversight of in vitro fertilization clinics, more detailed documentation of clinical trials for genome editing, and stronger integration of bioethics into education.

Experts have made the following statements about Dr. He’s work and its potential impacts:

  • Jennifer Doudna, (Professor of Chemistry and Molecular and Cell Biology, developer of CRISPR-Cas9 genome editing technology, University of California, Berkeley), statement, Nature, November 30, 2018: “The thought I kept having was the potential for rogue scientists to use this in unethical ways. It’s a real risk.”
  • Francis Collins (Director of United States National Institutes of Health), statement, November 28, 2018: “The need for development of binding international consensus on setting limits for this kind of research, now being debated in Hong Kong, has never been more apparent.”
  • Robin Lovell-Badge (research group leader, Francis Crick Institute), statement, Nature, November 27, 2018: “I’m worried about a knee-jerk reaction that might cause countries still working on regulations to make it unnecessarily hard to do this research.”

Beyond the response to Dr. He’s work, other discussions at the summit may influence future clinical research and government regulations on the global scale. In a concluding statement, the summit’s organizing committee stated that regulation of clinicians who run clinical trials, as well as cooperation with patient advocacy groups, may enable future clinical research on germline editing. The committee also identified the importance of international collaboration on a set of shared guidelines and internal communication with the public in establishing future government regulations.