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Science

Dawn of the designer babies? Here's an idiot's guide to human gene editing

Human gene editing tools have existed for years, raising hopes of preventing incurable diseases. These tools are now coming to fruition. So it's high time we learned more about our brave new world.

What is human gene editing?

Gene editing is a broad field in science. When it comes to human gene editing, we're talking about changing human DNA - the building blocks that make us who we are as individuals. Researchers hope the technology will one day allow us to quickly and precisely alter, or cut out, "rogue" genes to stamp out hereditary diseases.

So what's all this talk of designer babies?

Well, imagine you're a parent to-be and you happen to know your family line bears an hereditary disease, such as Huntington's, a neurodegenerative disease. There is no cure for Huntington's disease. But if you could remove the responsible genes from your unborn child, you could prevent their developing it. With some illnesses, you would have to edit thousands of genes, but still the concept is gaining support.

However, some say this sort of intervention is our "playing God." It's like the debate over other reproductive interventions, such as in-vitro fertilization (IVF), or stem cell research.

Why are people worried? Don't we all want to live longer?

People are worried because, as with so much in science, the full potential of the technology is not yet known. But a specific area of concern is "germline modification."

Germline modification involves editing the genetic makeup of embryos and sperm. And the fear - and the truth - is that such modifications would not only affect the person being treated, but their offspring, too. It would alter future generations.

Some people object to human gene editing, saying it will create risks for future generations, and as it's impossible to obtain consent from future generations, some say we have no right to be tinkering with those future lives.

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Do ethical concerns outweigh the potential to prevent incurable diseases with human gene editing?

It's the tip of an ethical minefield.

Ethics? I thought it was about preventing diseases?

It is about preventing diseases. The technology could help prevent hereditary diseases such as cystic fibrosis, Huntington's disease, and forms of cancer, for instance. Some scientists have reported success in experiments with sickle-cell anemia and HIV. Others are using these same principles to edit the genetic makeup of mosquitos - they have developed a "malaria-blocking gene" which, once tested in the wild, they hope will spread through mosquito populations and "disable" future generations from carrying and therefore spreading the disease.

The question is, where will it all stop? Some people fear we'll be unable to resist the temptation of changing the color of our baby's eyes or even the color of their skin once we get the tools out and start "pimping" genes to prevent incurable diseases.

And it stands to reason. We've yet to work out where to stop with plastic surgery, so why wouldn't we have the same problem with human gene editing? Plastic surgery is used to reconstruct people's faces, such as the volunteer firefighter in New York who received a full face transplant earlier this year, but it's also used widely for purely cosmetic reasons.

Hold on, you mentioned tools? What tools?

There are three main gene editing tools scientists are currently toying with - tools that allow them to edit genes in living cells much the same way as I'm editing these words as I write - I cut, paste, copy, delete, undo, and repeat.

CRISPR-Cas9

The most common tool at the moment is called CRISPR-Cas9, as it relies on the protein Cas9. Cas9 attacks the DNA of viruses like a pair of scissors. The CRISPR-Cas9 tool has been known to cut the wrong section of DNA, raising fears over its safety. But it is relatively cheap and easy to use, even in multi-gene experiments.

Zinc-finger nuclease

Another editor goes by the name of zinc-finger nuclease (ZFN). In trials, ZFNs were used to "engineer a specific gene deletion" into white blood cells (CD4+ T cells), and when successful, the edit disrupted the "door through which HIV enters cells" to attack the human immune system, as reported in the scientific journal Nature Methods.

ZFNs were the first genome editing tool. But its scope is limited, as it relies on proteins that are difficult to adapt for new gene targets. And it's prone to "off-target" cuts.

TALENs

Then there are TALENs. As with the others, TALENs are a protein, consisting of a "DNA-cutting enzyme" and a "DNA-grabbing region" that can be programmed for specific gene editing duties. TALENs are easier to program than ZFNs, and cheaper, but they also lack precision at times. That said, physicians at London's Great Ormond Street Hospital used TALENs in a "medical first" in June to treat a one-year-old girl suffering from leukemia.

Well, that's good. So, remind me, what's the problem?

Even scientists who agree there are benefits to be derived from human gene editing say we need to be clear about how quickly we proceed. George Church, a geneticist at Harvard University, is often cited for his work into xenotransplants - that is, deriving organs for humans from non-human donors, such as pigs, to create a reliable supply of organs for human transplant. Church and his colleagues say they used the CRISPR-Cas9 editing tool to modify pig embryos and inactivate 62 retroviruses, which are impossible to otherwise treat or neutralize. So before this, we wouldn't have been able to use pig organs in humans, even in sheer desperation, as the retroviruses could have caused human infection. Church's research has effectively lifted this barrier. But the problem is, many people would rather die than receive an organ from a pig. Would you accept a pig organ? I'm not so sure myself.

So there are ethical, social, and religious issues to be chewed through, even as researchers in different parts of the world plough on in this field as befits their local ideologies. As a result, there's a growing call for international guidelines on human gene editing.

But that's the question: is international consensus realistic?

Well, that's what researchers, policy makers, civil and human rights advocates, and the public are trying to work out. A large number of scientists and policy experts have been meeting this week in Washington D.C. at the International Summit on Human Gene Editing (December 1-3). Meanwhile in Berlin on Thursday (December 3) the German Ethics Council and National Academy of Sciences Leopoldina have been discussing ethics in an increasingly globalized science world.

As yet there is no international consensus on human gene editing. It's the same as with stem cell research - some countries allow it and others don't, and the reasons are many and varied.

In an opinion piece in The Guardian newspaper, John Harris, Professor Emeritus in Science Ethics at the University of Manchester, refers to Article 1 of the Universal Declaration on the Human Genome and Human Rights as "absurdly endorsing the notion of the preservation of the human genome as common heritage of humanity." He also criticizes Article 13 of the Council of Europe's Oviedo Convention for failing to explain how any genetic modification could be made without modifying the genome of any descendents (one of its requirements for allowing "preventative, diagnostic or therapeutic purposes").

These conventions do, nonetheless, take a position on the issue - and that on an international level. So perhaps in future we'll just have to spend a little more time modifying them as well as our DNA.

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