Journal Nature reports Chinese scientists have genetically modified human embryos with 32.5% success rate

In a world first, Chinese scientists have reported editing the genomes of human embryos. The results are published in the online journal Protein and Cell and confirm widespread rumours that such experiments had been conducted—rumours that sparked a high-profile debate last month about the ethical implications of such work.

In the paper, researchers led by Junjiu Huang, a gene-function researcher at Sun Yat-sen University in Guangzhou, tried to head off such concerns by using ‘non-viable’ embryos, which cannot result in a live birth, that were obtained from local fertility clinics. The team attempted to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder, using a gene-editing technique known as CRISPR/Cas9. The researchers say that their results reveal serious obstacles to using the method in medical applications.

“I believe this is the first report of CRISPR/Cas9 applied to human pre-implantation embryos and as such the study is a landmark, as well as a cautionary tale,” says George Daley, a stem-cell biologist at Harvard Medical School in Boston. “Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes.

Some say that gene editing in embryos could have a bright future because it could eradicate devastating genetic diseases before a baby is born. Others say that such work crosses an ethical line: researchers warned in Nature in March that because the genetic changes to embryos, known as germline modification, are heritable, they could have an unpredictable effect on future generations. Researchers have also expressed concerns that any gene-editing research on human embryos could be a slippery slope towards unsafe or unethical uses of the technique.

The team injected 86 embryos and then waited 48 hours, enough time for the CRISPR/Cas9 system and the molecules that replace the missing DNA to act — and for the embryos to grow to about eight cells each. Of the 71 embryos that survived, 54 were genetically tested. This revealed that just 28 were successfully spliced, and that only a fraction of those contained the replacement genetic material. “If you want to do it in normal embryos, you need to be close to 100%,” Huang says. “That’s why we stopped. We still think it’s too immature.”

His team also found a surprising number of ‘off-target’ mutations assumed to be introduced by the CRISPR/Cas9 complex acting on other parts of the genome.

A Chinese source familiar with developments in the field said that at least four groups in China are pursuing gene editing in human embryos.

An interview with Geoffrey Miller, an evolutionary psychologist and lecturer at NYU, at Vice shows that there is a difference in cultural attitude to genetic enhancement of children between Asia and the West

We have ideological biases that say, “Well, this could be troubling, we shouldn’t be meddling with nature, we shouldn’t be meddling with God.” I just attended a debate in New York a few weeks ago about whether or not we should outlaw genetic engineering in babies and the audience was pretty split. In China, 95 percent of an audience would say, “Obviously you should make babies genetically healthier, happier, and brighter!” There’s a big cultural difference.

There was other progress identifying the genes to enhance intelligence

Molecular Psychiatry – Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32.

The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10−17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer’s disease: TOMM40, APOE, ABCG1 and MEF2C.

Stephen Hsu posted on the main genetic findings on intelligence. Stephen Hsu has written extensively on the genetic basis on intelligence and the near future of embryo selection. Stephen advises BGI the main genomics company of China.

There was a review of five years of genome-wide association studies in 2011.

Scientists looking for the genes underlying intelligence are in for a slog. One of the largest, most rigorous genetic studies of human cognition1 has turned up inconclusive findings, and experts concede that they will probably need to scour the genomes of more than 1 million people to confidently identify even a small genetic influence on intelligence and other behavioural traits. The results were published in the Journal Nature.

In a 2013 study comparing the genomes of more than 126,000 people, the group identified three gene variants associated with with how many years of schooling a person had gone through or whether they had attended university. But the effect of these variants was small — each variant correlated with roughly one additional month of schooling in people who had it compared with people who did not.

In another study of 106,000 people, researchers picked out 69 gene variants most strongly linked to education level. To establish a more direct link with IQ, they cross-checked this list with genetic variants in a second sample of 24,000 people who also had taken tests of cognitive ability. Three gene variants were found to be associated with both educational attainment and higher IQ scores.

The three variants the researchers identified were each responsible for an average of 0.3 points on an IQ test. (About two-thirds of the population score between 85 and 115.) That means that a person with two copies of each variant would score 1.8 points higher on an intelligence test than a person with none of them.

To put those figures in perspective, those variants have about one-twentieth the influence on intelligence as do gene variants linked to other complex traits such as height, says Daniel Benjamin, a social scientist at Cornell University in Ithaca, New York, who co-led the study.

Benjamin says that studies of more than 1 million people will be needed to find enough common gene variants to explain 15% of the variation across people in IQ scores, educational attainment and other behavioral traits.

Selecting for intelligence or genetically engineering for intelligence will require larger studies to identify the genes and more genes will need to be altered to achieve the enhancement

I gave a talk at Transhuman Visions early in 2014.

In my look at near term transhumanism, I see older Tiger Moms as being the driver of early adoption of genetic intelligence enhancement and the lifting of the One child policy in China.

China’s One child policy is being lifted just as embryo selection based upon intelligence for invitro fertilized (IVF) babies becomes possible and we are on the cusp of genetic engineering. Women in China who are now older were banned from having babies but now will be allowed to have children. Many will not be able to conceive naturally and will use IVF. I see IVF going from 400,000 per year worldwide to 2-8 million per year over the next 10 years. IVF babies are more easily embryo selected and accessible for genetic modification. This would provide an economic boost to China in 20-30 years and the beginnings of a significant societal shift.

* Older women use IVF more than younger women.
* Societal shifts that cause more older women to use IVF to have children means more opportunity for embryo selection and genetic intelligence enhancement.
* Countries that permit embyro selection and genetic intelligence enhancement provide the opportunity for IVF to be used for enhancement
* Medical tourism to permissive countries is another means for older women to use IVF in combination with embryo selection or genetic enhancement.

In my talk I first summarized enhancement of human capabilities via products that we can buy. (Smartphones, Google Glass, Apple Siri, IBM Watson, forklifts, cars etc…) As those things get better, anyone can adopt them by buying the latest versions.

Steroids do enhance performance. They work. About 10 million people use them and it is primarily because of vanity. However, we do not live in the wild west or have to compete as Gladiators in Rome. The more powerful people in the world are the billionaires. In the real world the equivalent of Montgomery Burns from the Simpsons has more power than the equivalent of Captain America. Burns can hire his own police force or mercenaries. It is his lawyers and lobbyists who do his work.

100 years ago it was vaccines that began altering the physical attributes of people in a meaningful way. It extended lifespans and improved health. Health improvement boosted productivity and GDP.

I make the case that studies show that more intelligence leads to better lives for people. They go to jail less. Their jobs are better and they divorce less.

Each one-point increase in a country’s average IQ, the per capita GDP was $229 higher. It made an even bigger difference if the smartest 5 percent of the population got smarter; for every additional IQ point in that group, a country’s per capita GDP was $468 higher. This is according to Are the Wealthiest Countries the Smartest Countries? (Heiner Rindermann, of the Chemnitz University of Technology, Psychological Science )

However, we can see the damage when intelligence is lower across large national populations.

48% of children in India are stunted. Diseases can leave brain damage when they do not kill. This reduces IQ points by 11-20 on average across the country. This makes India more poor.

Embryo Selection

* In Vitro Fertilization (IVF) currently is used for 400,000 babies each year.
* A new “Alka Seltzer method” for controlling PH reduces costs from $10K-20K in developed world to about $1K
* Developing world was $2-4K and can be $200
* Comprehensive Chromosome Screening (about $6000) can boost successful IVF by 10-20%

–> Lower costs for IVF means more adoption and widespread basic genetic screening via chromosome screening will already be used for high IVF success rate

* China lifting one child ban
* This will mean annual birthrates will go from about 16 million ==> 25.5 million
* 23-42 normal child bearing age
* IVF at older ages up to 50-55 now at about 5-15% but improving
* More older women in China will use IVF
* China is not culturally against enhancing children (a lot of tiger moms and cultural differences)
* Lower cost and more effective IVF with standard chromosome screening, easy step to gene screening
* Maybe 4 million IVF/year with gene screening

Children tend to fall within a spread of 13 IQ points above and below the average IQ of their parents.
Positive outlier at around 2 or 3 percent where child is two standard deviations above parents
Pick the smartest genome from a batch of, say, 20 embryos (but it could 50 or more embryos) to get 20-30 IQ points higher
We are technologically close to non-destructive sequencing of human gametes and zygotes by sequencing 10-20 cells.

Genetic Engineering for Intelligence

BGI (Beijing Genomics institute has a large intelligence study of thousands of geniuses
Various studies finding genes with up to 0.5% impact on intelligence
Intelligence is 40-80% inheritable
There are likely hundreds to a thousand thousands to tens of thousands of genes that genetically determine intelligence
This is twenty times more complex than height. According to Steve Hsu’s estimates (based on actual data) most humans have (order of magnitude) 1000 rare (-) alleles for height. So about 20,000 rare alleles for intelligence.

One standard deviation above average has (very roughly) 30 fewer (-) variants.
No negative alleles might be 30 SD above average! Such a person has yet to exist in human history…
Each standard deviation (SD) up or down are defined as 15 IQ points greater or less,
95 percent of the population scores an IQ between 70 and 130, which is within two standard deviations of the mean.
30 SD above average would be and IQ of 550.

Maybe IQ 550 is Impossible or Meaningless

550 IQ would be like a 13 foot tall person
Physiology limits practical height
What are intelligence limits ?
Brain structure
Average human height is 70 inches and 3 inch SD (standard deviation)
8 feet 1 inch – 97 inches this is 9 Standard Deviations over average
235 IQ is the equivalent in intelligence of a 8 foot 1 inch person

Geniuses and Society

5% of population with 30 points higher intelligence might be about $14000 more GDP per capita
5% of population with 120 points higher intelligence might be about $56000 more GDP per capita
What would a society with tens of millions of Edisons, Einsteins, Steve Jobs and Elon Musks be like ?
Could we get beyond them in capability?

5% of population significantly intelligence enhanced would be possible if IVF takes off and embryo selection and genetic engineering with it over the next 10-20 years.

Journal Nature reports Chinese scientists have genetically modified human embryos with 32.5% success rate

In a world first, Chinese scientists have reported editing the genomes of human embryos. The results are published in the online journal Protein and Cell and confirm widespread rumours that such experiments had been conducted—rumours that sparked a high-profile debate last month about the ethical implications of such work.

In the paper, researchers led by Junjiu Huang, a gene-function researcher at Sun Yat-sen University in Guangzhou, tried to head off such concerns by using ‘non-viable’ embryos, which cannot result in a live birth, that were obtained from local fertility clinics. The team attempted to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder, using a gene-editing technique known as CRISPR/Cas9. The researchers say that their results reveal serious obstacles to using the method in medical applications.

“I believe this is the first report of CRISPR/Cas9 applied to human pre-implantation embryos and as such the study is a landmark, as well as a cautionary tale,” says George Daley, a stem-cell biologist at Harvard Medical School in Boston. “Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes.

Some say that gene editing in embryos could have a bright future because it could eradicate devastating genetic diseases before a baby is born. Others say that such work crosses an ethical line: researchers warned in Nature in March that because the genetic changes to embryos, known as germline modification, are heritable, they could have an unpredictable effect on future generations. Researchers have also expressed concerns that any gene-editing research on human embryos could be a slippery slope towards unsafe or unethical uses of the technique.

The team injected 86 embryos and then waited 48 hours, enough time for the CRISPR/Cas9 system and the molecules that replace the missing DNA to act — and for the embryos to grow to about eight cells each. Of the 71 embryos that survived, 54 were genetically tested. This revealed that just 28 were successfully spliced, and that only a fraction of those contained the replacement genetic material. “If you want to do it in normal embryos, you need to be close to 100%,” Huang says. “That’s why we stopped. We still think it’s too immature.”

His team also found a surprising number of ‘off-target’ mutations assumed to be introduced by the CRISPR/Cas9 complex acting on other parts of the genome.

A Chinese source familiar with developments in the field said that at least four groups in China are pursuing gene editing in human embryos.

An interview with Geoffrey Miller, an evolutionary psychologist and lecturer at NYU, at Vice shows that there is a difference in cultural attitude to genetic enhancement of children between Asia and the West

We have ideological biases that say, “Well, this could be troubling, we shouldn’t be meddling with nature, we shouldn’t be meddling with God.” I just attended a debate in New York a few weeks ago about whether or not we should outlaw genetic engineering in babies and the audience was pretty split. In China, 95 percent of an audience would say, “Obviously you should make babies genetically healthier, happier, and brighter!” There’s a big cultural difference.

There was other progress identifying the genes to enhance intelligence

Molecular Psychiatry – Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32.

The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10−17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer’s disease: TOMM40, APOE, ABCG1 and MEF2C.

Stephen Hsu posted on the main genetic findings on intelligence. Stephen Hsu has written extensively on the genetic basis on intelligence and the near future of embryo selection. Stephen advises BGI the main genomics company of China.

There was a review of five years of genome-wide association studies in 2011.

Scientists looking for the genes underlying intelligence are in for a slog. One of the largest, most rigorous genetic studies of human cognition1 has turned up inconclusive findings, and experts concede that they will probably need to scour the genomes of more than 1 million people to confidently identify even a small genetic influence on intelligence and other behavioural traits. The results were published in the Journal Nature.

In a 2013 study comparing the genomes of more than 126,000 people, the group identified three gene variants associated with with how many years of schooling a person had gone through or whether they had attended university. But the effect of these variants was small — each variant correlated with roughly one additional month of schooling in people who had it compared with people who did not.

In another study of 106,000 people, researchers picked out 69 gene variants most strongly linked to education level. To establish a more direct link with IQ, they cross-checked this list with genetic variants in a second sample of 24,000 people who also had taken tests of cognitive ability. Three gene variants were found to be associated with both educational attainment and higher IQ scores.

The three variants the researchers identified were each responsible for an average of 0.3 points on an IQ test. (About two-thirds of the population score between 85 and 115.) That means that a person with two copies of each variant would score 1.8 points higher on an intelligence test than a person with none of them.

To put those figures in perspective, those variants have about one-twentieth the influence on intelligence as do gene variants linked to other complex traits such as height, says Daniel Benjamin, a social scientist at Cornell University in Ithaca, New York, who co-led the study.

Benjamin says that studies of more than 1 million people will be needed to find enough common gene variants to explain 15% of the variation across people in IQ scores, educational attainment and other behavioral traits.

Selecting for intelligence or genetically engineering for intelligence will require larger studies to identify the genes and more genes will need to be altered to achieve the enhancement

I gave a talk at Transhuman Visions early in 2014.

In my look at near term transhumanism, I see older Tiger Moms as being the driver of early adoption of genetic intelligence enhancement and the lifting of the One child policy in China.

China’s One child policy is being lifted just as embryo selection based upon intelligence for invitro fertilized (IVF) babies becomes possible and we are on the cusp of genetic engineering. Women in China who are now older were banned from having babies but now will be allowed to have children. Many will not be able to conceive naturally and will use IVF. I see IVF going from 400,000 per year worldwide to 2-8 million per year over the next 10 years. IVF babies are more easily embryo selected and accessible for genetic modification. This would provide an economic boost to China in 20-30 years and the beginnings of a significant societal shift.

* Older women use IVF more than younger women.
* Societal shifts that cause more older women to use IVF to have children means more opportunity for embryo selection and genetic intelligence enhancement.
* Countries that permit embyro selection and genetic intelligence enhancement provide the opportunity for IVF to be used for enhancement
* Medical tourism to permissive countries is another means for older women to use IVF in combination with embryo selection or genetic enhancement.

In my talk I first summarized enhancement of human capabilities via products that we can buy. (Smartphones, Google Glass, Apple Siri, IBM Watson, forklifts, cars etc…) As those things get better, anyone can adopt them by buying the latest versions.

Steroids do enhance performance. They work. About 10 million people use them and it is primarily because of vanity. However, we do not live in the wild west or have to compete as Gladiators in Rome. The more powerful people in the world are the billionaires. In the real world the equivalent of Montgomery Burns from the Simpsons has more power than the equivalent of Captain America. Burns can hire his own police force or mercenaries. It is his lawyers and lobbyists who do his work.

100 years ago it was vaccines that began altering the physical attributes of people in a meaningful way. It extended lifespans and improved health. Health improvement boosted productivity and GDP.

I make the case that studies show that more intelligence leads to better lives for people. They go to jail less. Their jobs are better and they divorce less.

Each one-point increase in a country’s average IQ, the per capita GDP was $229 higher. It made an even bigger difference if the smartest 5 percent of the population got smarter; for every additional IQ point in that group, a country’s per capita GDP was $468 higher. This is according to Are the Wealthiest Countries the Smartest Countries? (Heiner Rindermann, of the Chemnitz University of Technology, Psychological Science )

However, we can see the damage when intelligence is lower across large national populations.

48% of children in India are stunted. Diseases can leave brain damage when they do not kill. This reduces IQ points by 11-20 on average across the country. This makes India more poor.

Embryo Selection

* In Vitro Fertilization (IVF) currently is used for 400,000 babies each year.
* A new “Alka Seltzer method” for controlling PH reduces costs from $10K-20K in developed world to about $1K
* Developing world was $2-4K and can be $200
* Comprehensive Chromosome Screening (about $6000) can boost successful IVF by 10-20%

–> Lower costs for IVF means more adoption and widespread basic genetic screening via chromosome screening will already be used for high IVF success rate

* China lifting one child ban
* This will mean annual birthrates will go from about 16 million ==> 25.5 million
* 23-42 normal child bearing age
* IVF at older ages up to 50-55 now at about 5-15% but improving
* More older women in China will use IVF
* China is not culturally against enhancing children (a lot of tiger moms and cultural differences)
* Lower cost and more effective IVF with standard chromosome screening, easy step to gene screening
* Maybe 4 million IVF/year with gene screening

Children tend to fall within a spread of 13 IQ points above and below the average IQ of their parents.
Positive outlier at around 2 or 3 percent where child is two standard deviations above parents
Pick the smartest genome from a batch of, say, 20 embryos (but it could 50 or more embryos) to get 20-30 IQ points higher
We are technologically close to non-destructive sequencing of human gametes and zygotes by sequencing 10-20 cells.

Genetic Engineering for Intelligence

BGI (Beijing Genomics institute has a large intelligence study of thousands of geniuses
Various studies finding genes with up to 0.5% impact on intelligence
Intelligence is 40-80% inheritable
There are likely hundreds to a thousand thousands to tens of thousands of genes that genetically determine intelligence
This is twenty times more complex than height. According to Steve Hsu’s estimates (based on actual data) most humans have (order of magnitude) 1000 rare (-) alleles for height. So about 20,000 rare alleles for intelligence.

One standard deviation above average has (very roughly) 30 fewer (-) variants.
No negative alleles might be 30 SD above average! Such a person has yet to exist in human history…
Each standard deviation (SD) up or down are defined as 15 IQ points greater or less,
95 percent of the population scores an IQ between 70 and 130, which is within two standard deviations of the mean.
30 SD above average would be and IQ of 550.

Maybe IQ 550 is Impossible or Meaningless

550 IQ would be like a 13 foot tall person
Physiology limits practical height
What are intelligence limits ?
Brain structure
Average human height is 70 inches and 3 inch SD (standard deviation)
8 feet 1 inch – 97 inches this is 9 Standard Deviations over average
235 IQ is the equivalent in intelligence of a 8 foot 1 inch person

Geniuses and Society

5% of population with 30 points higher intelligence might be about $14000 more GDP per capita
5% of population with 120 points higher intelligence might be about $56000 more GDP per capita
What would a society with tens of millions of Edisons, Einsteins, Steve Jobs and Elon Musks be like ?
Could we get beyond them in capability?

5% of population significantly intelligence enhanced would be possible if IVF takes off and embryo selection and genetic engineering with it over the next 10-20 years.