Genetic mutations aren't harmful

When will the genetically optimized super humans come?

CRISPR made it easier to manipulate DNA. In addition, steadily growing genetic data sets reveal which variations in the genetic make-up could be partly responsible for human characteristics. Do both together mean that genetically optimized humans will soon be possible? We want to know this and more from the geneticist Wolfgang Nellen.

An interview by Wolfgang Kerler

Perhaps we will be considered the ancestors of the really go down in history for modern humans. As a species whose specimens were seldom perfect. Some could run quickly, others were good at arithmetic, some grew old, many died prematurely. This is what superpeople of the 22nd century could find out about their ancestors in historical documentation - and wonder about it. If only they would all be smart, sporty, healthy and genetically optimized.

Sounds like Science fiction. But since the Chinese researcher He Jiankui announced in November 2018 that they had created the first CRISRP babies, such a future seems entirely plausible. He said he had modified the CCR5 gene in the two girls' embryos to make them immune to HIV. After all, CCR5 is considered to be the gateway for the virus. He Jiankui used the CRISPR / Cas method, often called “gene scissors”. Since such experiments on humans are also illegal in China, he and three of his colleagues have now been sentenced to several years in prison.

Are Genes Responsible for Wealth and Income?

Also the results of Genome-Wide Association Studies, GWAS for short, keep making exciting headlines. Would you like an example? "Scientists find 24 'golden' genes that help us get rich," wrote the Sunday Times in spring 2019. The article was about research by a team led by Scottish geneticist David Hill looking for gene variants that are linked to commercial success.

To do this, Hill and his colleagues used the UK Biobank, the largest genetic database in the world. In it, they found the genetic data of 286,000 participants who had also provided information on their household income. The scientists looked for gene variants that are particularly common with high incomes at 18 million locations in the genome of these people. They found what they were looking for in around 30 places and, according to their own statements, were able to relate this to 7.4 percent of the income gap. Conversely, this means that they did not find any correlations in the genome for 92.6 percent of the differences.

The debate that began after the publication of the controversial study ultimately fundamentally called into question the purpose of Genome-Wide Association Studies. What is the point of looking for explanations for certain properties in the growing mountains of human genetic data? Can GWAS localize the genetic causes of human "weaknesses" that can be "CRISPRted" away in future generations? Or are you just finding useless correlations?

We wanted to know that too - and were able to ask an expert from the 1E9 community: Wolfgang Nellen. The professor of genetics at the University of Kassel has now retired, but is a co-founder of the Science Bridge association, which aims to bring genetic experiments to schoolchildren and non-scientists. Wolfgang Nellen is registered as @serigala at 1E9. He is happy to answer any further questions from the community!

1E9:You slowly get the feeling that our genes explain everything.Whether we can dance or not,whether we like dogs or notwhether we get rich or not. As a geneticist, you should be happy about that, right?

Wolfgang Nellen: Above all, I find it extremely interesting what is being pushed onto the genome. Even politics reporting discovered the DNA. I keep reading sentences like: “This is in the DNA of the SPD” or in the DNA of physicists, the Fridays for Future movement or the sausage seller. This shows that we are also experiencing a phase in the media in which a strong genetic predetermination is assumed. The impression arises that we don't have to do anything in our life, because everything is predetermined by our genes anyway.

I still remember very different times. If I had said in my early days as a lecturer that certain things are genetic, I would probably have been stoned. In the 1960s and 70s, genetics was only for peas or flies. Humans were considered a blank slate - and their environment was made responsible for everything, whether for intelligence or social characteristics.

And what is the current state of science? Do our genes or our environment determine who and how we are?

Wolfgang Nellen: The answer is: both. How high the share of genetics and the share of the environment is, however, is very difficult to say.

What are Genome-Wide Association Studies?

GWAS are often performed to find connections between certain gene variations and certain physical or social characteristics. The entire genome is examined, hence the name: genome-wide association study.

This requires, on the one hand, DNA samples from study participants and, on the other hand, information about specific characteristics of the participants. The datasets that researchers can access for GWAS are getting bigger and bigger - also thanks to start-ups like 23andMe, which have been offering affordable DNA tests for a few years.

The extensive Genome-Wide Association Studies should also provide more precise information. However, they are repeatedly criticized. What do you think of GWAS?

Wolfgang Nellen: I think GWAS are a great method. You just have to know where their limits are. Above all, you always have to be aware that you are talking about correlations - and correlations are different from causalities.

I recall the relationship between the number of storks and the birth rate. There you can find wonderful correlations, as there are not only more storks in the country, but - in relation to the number of inhabitants - also more babies. Of course, one could conclude from this that the stork brings the children. But it is not right.

The problem with the GWAS is that they tend to be over-interpreted in a populist way. However, they allow a hypothesis that can be tested experimentally.

So the study recently published by David Hill and his team does not suggest that specific gene variants are responsible for wealth. So is it an example of a superfluous GWAS?

Wolfgang Nellen: I don't find the correlation between income and genetics that dreadfully stupid. At first I laughed and thought: What's the nonsense? On closer inspection, however, I found the result very interesting, albeit almost trivial. The "wealth genes" found there overlap with the "intelligence genes" identified by other GWAS. Statistically speaking, the connection between intelligence and income is not entirely nonsensical.

You have emphasized the quotation marks around “wealth genes” and “intelligence genes” again. Why?

Wolfgang Nellen: Because we are only talking about correlations here, too. Certain gene variants are more common in people who are rich or - as we define them today - intelligent. I see these results from GWAS studies as a starting point for further investigations. They should clarify what exactly is behind it and whether there is actually a causal connection.

CRISPR / Cas: The revolutionary "gene scissors"

The CRISRP / Cas method, scientifically described for the first time in 2012, is also called “gene scissors”. To put it simply, it can be used to control a certain DNA segment in a living cell and cut it (relatively) precisely. At precisely this point, individual “letters” (bases) of the DNA can be exchanged, inserted or removed. It is also possible to delete or add entire genes. The genetic information is rewritten or "edited".

Let us assume that a causal relationship is found between gene variants and intelligence. Then it should be possible to optimize embryos using CRISPR / Cas in such a way that the children become intelligent and rich, right? He Jiankui finally proved that CRISPR babies are possible.

Wolfgang Nellen: It does not work so fast. You will not be able to simply say: My child will later become incredibly rich because I gave him the "rich gene" or the "intelligence gene". Because we're talking about individual genes that contribute less than one percent to the trait “wealth” or “intelligence”.

A great many genes have been found that could be related to what we define as intelligence. One of the popular studies speaks of 300, another even of 1000 genes. A single gene may account for 0.1 percent of intelligence. “Optimizing” a gene would therefore hardly be of any use. Maybe ten genes will get more out of it. But maybe all of these genes have to be present in a very specific combination.

We are still a long way from understanding these networks precisely and identifying the contribution of individual genes. But I think that certain "optimizations" could be possible in the long term. There will definitely be further attempts.

However, the scientist who created the first “optimized” CRISPR babies is now in prison.

Wolfgang Nellen: Yes. But from now on the children will be constantly monitored and analyzed down to the bone, I'm sure. If the experiment was successful, it will be known in five or six years. Maybe even sooner. This could also lead to a boom in optimization attempts because He Jiankui may not have been talking about HIV resistance at all.

What makes you think that?

Wolfgang Nellen: I like to be a bit of an aluminum hat carrier. But I have my doubts that He Jiankui was primarily concerned with HIV. Finally there is therapy for HIV.

I think he might actually have been trying to optimize the two girls' memories. The affected gene CCR5 has the complex property of many genes: it is multifunctional. On the one hand, CCR5 is the gateway for HIV or the smallpox virus. But the mutation of CCR5 also ensures better nerve regeneration in humans after a stroke. And in experiments with mice it was found that a mutation in the CCR5 gene gave them a better memory.

Regardless of what He Jiankui was actually about, his approach was criticized as unethical even in China. Couldn't that prevent further optimization attempts?

Wolfgang Nellen: Whether further research is seen as ethically justifiable or not, as I hang out the window a bit, will depend on whether He Jiankui's experiment worked to some extent. If the girls' memory has improved even slightly, an optimization boom can hardly be prevented.

So when could the age of genetically optimized humans begin? After all, there is constant progress in CRISPR and similar methods. And GWAS constantly supplies new potential target genes that could be “optimized”.

Wolfgang Nellen: I believe the age of trying to optimize has already begun. We will probably only know in 30 or 40 years whether this will really be successful - but maybe even sooner.

If you want to deal more intensively with the question of how genetic engineering will change the future of our species, you can register for a free scenario workshop that will take place on February 5, 2020 in the Museum für Naturkunde. The research project "Zukunft Mensch" and the CRISPR-Whisper project of the Science Bridge invite you to the thought experiment. Wolfgang Nellen will also be there. He will also give a lecture on March 21, 2020 with the title “CRISRPCas - The Gene Scissors Explained” in the Mikrotarium Berlin, for which you can also register for free now.

All members of the 1E9 community are welcome to ask Wolfgang Nellen alias @serigala further questions about genetic engineering, CRISPR and GWAS!

Cover picture: Andrew Brookes / Getty Images