Editing Human DNA: Risks, Ethics and the 2015 Gene Editing Summit

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The Risks and Ethics of Editing Human DNA: The 2015 Summit

Editing human DNA is risky and ethically fraught mainly when the changes would be inherited. Altering a patient's own body cells to treat a disease is now an approved medical treatment, but editing eggs, sperm or embryos would pass changes, and any mistakes, to every later generation. That line between treating one person and changing heredity is exactly what scientists argued over at the first International Summit on Human Gene Editing in Washington, D.C., on 1 to 3 December 2015.

Below is what the summit discussed, what it decided, what has happened since, and where the real risks and the overblown fears lie.

Why the 2015 summit was called

The trigger was a technique called CRISPR-Cas9. In 2012 teams led by Jennifer Doudna at UC Berkeley and Emmanuelle Charpentier, then at Umeå University, showed that a bacterial enzyme could be guided by a short piece of RNA to cut DNA at a chosen spot. Once a cell's DNA is cut, its own repair machinery can be steered to disable a gene or patch in a new sequence. Older methods existed, but CRISPR made precise edits cheap and quick enough for an ordinary laboratory. Doudna and Charpentier shared the 2020 Nobel Prize in Chemistry for the work.

In April 2015 a team in China reported the first attempt to edit human embryos with CRISPR. They used embryos that could never develop into a baby and tried to correct the gene behind beta thalassaemia, a blood disorder. The results were sobering: only 4 of 54 embryos carried the intended change, those were mosaics (some cells edited, some not), and the enzyme had also cut DNA in places it should not have. The paper made it clear that heritable editing was no longer a thought experiment.

The US National Academy of Sciences and National Academy of Medicine therefore organised the summit with the Chinese Academy of Sciences and the UK's Royal Society. Around 500 scientists, doctors, ethicists, lawyers, historians and patient advocates attended. Nobel laureate David Baltimore of Caltech, who chaired the organising committee, opened by saying, "We could be on the cusp of a new era in human history."

Somatic and germline editing: the key distinction

Almost every argument at the summit turned on two kinds of editing:

  • Somatic editing changes cells in one person's body, such as blood stem cells or cells in the eye. The effects end with that patient. Ethically it resembles other new treatments: it needs evidence that it is safe and works, and the patient's consent.
  • Germline editing changes eggs, sperm or early embryos. Every cell of the resulting child carries the edit, including that child's own eggs or sperm, so the change can pass down the family line.

Germline editing was the hard question. Supporters pointed to families carrying serious inherited diseases such as Huntington's disease, cystic fibrosis or Tay-Sachs disease, and argued that it would be wrong to refuse a tool that could spare future children. Critics answered that most such families can already avoid passing on a disease by screening embryos during IVF, so the medical need is narrower than it sounds. Harvard geneticist George Church warned that "enhancement" would likely creep in through the door of disease treatment, once the methods became routine.

The main risks scientists raised

Off-target and incomplete edits

CRISPR can cut similar-looking stretches of DNA elsewhere in the genome. In a single patient, an unwanted change might cause harm to that person; in an embryo it could create a new disorder that is then inherited. Mosaicism is a second problem, because a child with a mix of edited and unedited cells may not get the intended benefit, and testing an embryo cannot easily reveal which cells were changed.

Effects we cannot predict

Many genes have more than one role. A change that protects against one disease could raise the risk of another, and the full consequences might only become clear decades later, in grandchildren who never agreed to the experiment.

Enhancement and fairness

Speakers worried about parents choosing traits such as height or intelligence. Most such traits depend on hundreds of genes and on environment, so "designer babies" remain far beyond current science. The fairness worry is still real: if any enhancement became possible, it would probably be available first to the wealthy, potentially widening inequality.

A global patchwork of rules

Countries regulated the area very differently. Some banned all embryo editing research, some allowed laboratory work but no pregnancies, and some had no specific rules. In the United States, the National Institutes of Health would not fund such research. John Holdren, then the White House science adviser, noted that what one country attempts "will have consequences in others."

What the summit decided

The organising committee did not call for a permanent ban. Its closing statement drew three lines:

  • Basic and preclinical research, including editing human embryos in the lab, should go ahead under proper oversight, as long as edited embryos are not used to start a pregnancy.
  • Somatic editing for patients could move into clinical trials under existing medical regulation.
  • Using germline editing to create a pregnancy would be irresponsible until the safety and effectiveness questions were resolved and there was broad agreement in society that a particular use was appropriate.

Baltimore said the statement was the organisers' answer to whether there should be a ban. In practice it was a call for restraint, with the door left open for the future.

What happened after the summit

In 2017 a committee of the two US National Academies said heritable editing might one day be acceptable, but only for serious conditions and under strict oversight. Then, in November 2018, the Chinese scientist He Jiankui announced that twin girls had been born from embryos he had edited to disable a gene called CCR5, aiming to make them resistant to HIV. He presented the work at the second international summit in Hong Kong days later. The reaction was almost universal condemnation: the twins were not at risk of a disease that could not be prevented by other means, and the editing was incomplete. A court in Shenzhen sentenced him on 30 December 2019 to three years in prison and a fine of 3 million yuan; he was released in April 2022. A third child edited in the same programme was born in 2019.

Somatic editing, meanwhile, became real medicine. In November 2023 the UK's medicines regulator authorised Casgevy, the first CRISPR-based therapy, for sickle cell disease and transfusion-dependent beta thalassaemia. The US Food and Drug Administration followed in December 2023 and January 2024. Doctors collect the patient's own blood stem cells, edit them so the body produces more foetal haemoglobin, and return them after high-dose chemotherapy. Nothing is passed to the patient's children. The treatment is demanding and costly, with a US list price of about $2.2 million.

Heritable editing has stayed off limits. Around 70 countries explicitly prohibit using edited embryos to start a pregnancy, and since 2016 a clause in US federal spending law has stopped the FDA from using its funds on research involving heritable modification of human embryos.

Common misconceptions about gene editing

"Gene editing means designer babies"

The approved uses of CRISPR treat individual patients and are not inherited. Complex traits are controlled by many genes and by upbringing, and no one knows how to engineer them.

"Editing is perfectly precise"

It is far more precise than older methods, but off-target cuts and mosaicism are still active research problems, which is why regulators require long follow-up of treated patients.

"Scientists simply decided it was fine"

The 2015 summit, and the meetings that followed, did the opposite: they set out conditions that heritable editing has not met, and the one person known to have ignored them went to prison.

Where Thinking Humanity stands

We think treating disease in consenting patients is a welcome use of this science. Changing the inheritance of people not yet born is different: the risks are unknown, the effects cannot be reversed, and the people most affected cannot be asked. Until those problems are solved, caution about editing the human germline is the wiser path, and the debate deserves to involve the public, not only laboratories. If you or your family live with an inherited condition, talk to a doctor or a genetic counsellor about the options that already exist.

Sources: US National Academies: International Summit on Human Gene Editing (2015); National Academies: Summit organisers' statement, 3 December 2015; Wikipedia: CRISPR gene editing; Wikipedia: Human germline engineering; Wikipedia: He Jiankui affair; MIT Technology Review: He Jiankui sentenced (2019); UK government: MHRA authorises Casgevy (2023); Wikipedia: Exagamglogene autotemcel (Casgevy); originally reported by I Heart Intelligence.

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