December 29, 2016

Predictions of human intelligence possible from DNA alone as we near effective embryo selection and gene editing of humans

Stephen Hsu at Infoproc reports that we now know enough about the genetic architecture of human intelligence to make predictions based on DNA alone. While it is a well-established scientific fact that variations in human cognitive ability are influenced by genes, many have doubted whether scientists would someday decipher the genetic code sufficiently to be able to identify individuals with above or below average intelligence using only their genotypes. That day is nearly upon us.

The figures below are taken from a recently published paper (see bottom), which examined genomic prediction on a longitudinal cohort of ~1000 individuals of European ancestry, followed from childhood into adulthood. (The study, based in Dunedin, New Zealand, extends over 40 years.) The genomic predictor (or polygenic score) was constructed using SSGAC GWAS analysis of a sample of more than one hundred thousand individuals. (Already, significantly more powerful predictors are available, based on much larger sample size.) In machine learning terminology, the training set includes over a hundred thousand individuals, and the validation set roughly one thousand.

These graphs show that individuals with higher polygenic score exhibit, on average, higher IQ scores than individuals with lower polygenic scores.

Effective embryo selection is nearing

  • The cost of embryo selection is modest, at $1500 + $200 per embryo, with the sequencing cost projected to drop rapidly. Embryo selection cost will drop in future
  • Embryo selection was unprofitable in late 2015 (mean: -$673) in the USA under the lowest estimate of the value of an IQ point, but profitable under the highest (mean: $4763). The main constraints on selection profitability is the polygenic score; under the highest value, the NPV EVPI of a perfect SNP predictor is $27b and the EVSI per education/SNP sample is $71k
  • Selection can be made much more profitable by selecting on multiple phenotype traits; selection scales near-linearly with equally-valuable traits, and considering an example using 7 traits (IQ / height / BMI / diabetes / ADHD / bipolar / schizophrenia), there is a gain of 2.8x over IQ alone ($4977 to about $14130)
The maximum amount of IQ gain if screening allowed for optimal selection

Chickens have become physically larger because of breeding and farming methods

In 2014, I gave a talk at Transhuman Visions in 2014 where I said older Tiger Moms would be the driver of early adoption of genetic intelligence enhancement after the lifting of the One child policy in China.

China's One child policy was 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.

IVF up over 50% in China since one child policy change

By December, 2015 there has been a 50 per cent jump in IVF consultations since the one-child policy announcement.

China is set to be the biggest IVF market in the world, probably within the next couple of years. Chinese couples who have the financial means often go abroad to the United States, Australia, Thailand and Vietnam for IVF. Rising Chinese demand for fertility treatments is also increasing IVF demand overseas clinics such as Australia-based Monash IVF Group and Virtus Health or Superior A.R.T. in Thailand, where 30-40 per cent of patients come from China.

Patient numbers are still climbing too. There were nearly half a million treatment "cycles" in 2013 at 356 approved clinics, compared with just under 200,000 cycles that year in the higher-value US market. Those levels were before the lifting of the one child policy.

Older women going for IVF

A 61-year-old woman has became what is believed to be China’s second oldest mother, according to media reports, in a growing trend of older births among desperate couples who have been left childless by Beijing’s draconian one-child policy.

The baby was born six days after media reported that another Chinese woman, 54-year-old Liu Hongmei, gave birth to a boy through IVF following the loss of her son in a traffic accident two years ago.

China reformed its strict family planning laws last October, but there are an estimated million Chinese families who have lost the only child they were ever allowed to have – including 335,000 mothers over 49.

Genetic screening embryos

A chinese woman gave birth to baby girl using an embryo frozen 18 years ago

Until recently fertility experts were only been able to judge the health of an embryo by its appearance.

A new test called Comprehensive Chromosomal Screening (CCS) is allowing fertility specialists to determine with much greater accuracy which embryos in IVF have the normal number of chromosomes and are the most likely to result in a successful pregnancy.

Studies have shown that IVF with CCS can achieve

• Pregnancy rates as high as 70%
• Miscarriage rate as low as 10%.
• A very low risk of chromosomal problems such as Down's syndrome (diagnostic accuracy of CCS is about 99%)

To further improve on the results of CCS, Olive Fertility is pioneering another technique for screening embryos with mitochondrial DNA quantification.

It appears that around a third of embryos with the correct number of chromosomes still fail to lead to a successful pregnancy. Recent studies have shown that embryos with a higher concentration of mitochondrial DNA have a reduced chance of implantation. Mitochondria are the energy producing engines within our cells, but surprisingly, an abundance of mitochondria appears to be associated with lower implantation potential.

The engineering is intended to switch on the immune response to attack cancer. In the pharmaceutical industry, antibody drugs directly blocking the PD-1 protein including Merck & Co.’s Keytruda and Opdivo sold by Bristol-Myers Squibb Co. have become new growth engines for the companies.

A study from the University of Oxford, which was recently presented at the annual meeting of the European Society of Human Reproduction and Embryology in Helsinki, suggested that screening embryos for their levels of mitochondrial DNA could help doctors select those that are most likely to result in a healthy pregnancy.

With CCS, an egg is fertilized in the laboratory and the embryo is grown for 5 days at which point 5-10 cells are taken from the part of the embryo that will form the placenta (thus leaving the cells that are destined to become the fetus untouched).

The embryo is then frozen and the biopsied cells are sent to a specialized laboratory for testing. The results usually return in 10-14 days identifying which embryos are chromosomally normal. A healthy embryo can be transferred in the next menstrual cycle.

Illumina offering pre-implantation next generation sequencing

Preimplantation genetic screening (PGS) determines the chromosomal status of an embryo by screening all 23 chromosome pairs prior to transfer in an IVF cycle. PGS enables the selection of embryos for transfer that are most likely to be free of chromosomal problems.

PGS is described in 8 pages and details how it is compatible with WHOLE GENOME sequencing and screening

Gene editing on humans

Chinese scientists are embarking on what appear to be the first human trials with the Crispr gene editing tool, the latest effort by the country’s researchers to master a technology that might someday be a potent tool in developing therapies worldwide.

Nature - Chinese scientists to pioneer first human CRISPR trial

Chinese scientists are on the verge of being first in the world to inject people with cells modified using the CRISPR–Cas9 gene-editing technique.

A team led by Lu You, an oncologist at Sichuan University’s West China Hospital in Chengdu, plans to start testing such cells in people with lung cancer next month. The clinical trial received ethical approval from the hospital's review board on 6 July.

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