Can We Handle the Truth in Our Genome?

There are tens of millions of women missing from global population, mostly in Asian countries like China, India, Afghanistan, but this phenomenon can be detected around the world [1]. Missing women are a difference of what we would expect based on random distribution of gender and what we actually see in populations [2,3].

The key reason behind this ‘gap’ appears to be parents’ cultural preference to male children resulting in various practices to skew the globally expected 1.05 boys to girls ratio. One of these practices is prenatal sex selection through the selective abortion of female foetuses - they are increasingly often ‘betrayed’ early on by their genome.

Very basic genetic test on the biopsy of chorion (part of placenta), reveals karyotype - number and appearance of chromosomes. Karyotype can detect some very serious genetic defects, e.g. Down syndrome, trisomy of chromosome 21. Lately, we are able to do this in a non-invasive way from mother’s blood, since it contains foetal DNA as well [4]. Almost as a side product of these tests we can know gender of the baby very early in pregnancy – famous XX for girls and XY for boys. Unfortunately, this seems to be adopted as a ‘discrete way’ to identify and terminate early pregnancies with girls in many places around the world [5].

The scale of this problem is truly depressing. Various researchers put a number of missing women anyway between 60 and 130 million [2,3,6]. Many of them are missing due to their treacherous second X chromosome.

This leads me to the troubling question:

If even basic analysis of our genome leads to such sinister and completely unexpected uses, what are then implications of next generation sequencing and genome editing technologies?

Our growing knowledge of the variants in human genome and more affordable sequencing allows us already to predict with reasonable accuracy various characteristic. These can be pathological or just variations in human diversity. But what if we are able to know these things before our children are born, or while they are still an embryo in the test tube? As we have seen above just knowing the gender can create quite a mess.

What other preferences for our children will we have if we have an option to choose? Would we opt for one expected to be taller, or one expected to have a certain colour of eyes, or higher IQ?

We can probably agree that we should know about highly pathological conditions like Cystic Fibrosis, or Huntington’s Chorea etc. Eye colour or height probably shouldn’t matter (may matter to some), but that leaves us with a huge grey area in between of uncertainty and various preferences which may be purely cultural or personal. How can we control these?

What if we are told that the child is more likely to be obese, or if has 15% chance of developing schizophrenia or autism? Should we do anything, and crucially should we even know, can we be trusted with this knowledge?

Looming behind the horizon is something even more exciting, brilliant technology for precise editing of genome – CRISPR. This technology has been making a lot if headlines, including recent high profile court battle for a lucrative patent [7].

Now we have an even more difficult challenge, it’s not just about knowing, but when should we interfere to change DNA – ours or of our children. This technology has already fuelled imagination about the designer babies and superhuman breeding scenarios [8]. Last year we already saw a first steps in editing human genome [9].

Just recently The National Academies of Sciences, Engineering and Medicine published recommendations for use of genome editing technologies in humans [10]. These recommendations seem reasonable, avoid editing heritable human genome except ‘for compelling purposes of treating or preventing serious disease or disabilities’.

But can recommendations like this really control the way we use such technology? Albert Einstain and Niels Bohr understood the potential of nuclear energy, but couldn’t really expect thousands of nuclear warheads spread around the world, including some in the hands of an unpredictable dictator of a rogue Asian nation. Nuclear technology was protected by the powerful armies, developing it takes industrial scale efforts, but still it is far from being under control. Then how can we control something that can be done in a lab smaller than your average restaurant?

Recommendations mentioned above may be acceptable, but they have limited reach and in one country only. By the time policy makers and regulators across the world catch up, I suspect that genome selecting and modifying genie may be out of the bottle.

Just for the record, I am certain that when used properly genomics and molecular biology in general can help many of us live longer and healthier lives. Big part of my daily work is developing and deploying technology to support and accelerate research and application of ‘omics’ based solutions. But, I also do think that we need to have a wider discussion on implications of these technologies, they may be far more profound than we think.

Please let me know your thoughts on this topic.

Opinions are my own.

1.     Bongaarts, J., & Guilmoto, C. Z. (2015). How many more missing women? Excess female mortality and prenatal sex selection, 1970–2050. Population and Development Review, 41(2), 241-269.

2.     Perianayagam, A., & Goli, S. (2012). Provisional results of the 2011 Census of India: slowdown in growth, ascent in literacy, but more missing girls. International Journal of Social Economics, 39(10), 785-801.

3.     Jiang, Q., Li, S., Feldman, M. W., & Sánchez-Barricarte, J. J. (2012). Estimates of Missing Women in Twentieth Century China. Continuity and Change, 27(3)

4.     Yu SCY, Jiang P, Choy KW, et al. (2103) Noninvasive Prenatal Molecular Karyotyping from Maternal Plasma. Shomron N, ed. PLoS ONE; 8(4):e60968.

5.     Madan, K., & Breuning, M. H. (2013). Impact of prenatal technologies on the sex ratio in India: an overview. Genetics in Medicine, 16(6), 425-432.

6.     Hudson, VM and den Boer, A (2005) Missing Women and Bare Branches: Gender Balance and Conflict. Environmental Change and Security Program Report (11). pp. 20-24.

7.     Ledford H, (2017) Broad Institute wins bitter battle over CRISPR patents. Nature News. [Online: https://www.nature.com/news/broad-institute-wins-bitter-battle-over-crispr-patents-1.21502]

8.     Editing humanity (2015) Economist. [Online: https://www.economist.com/news/leaders 21661651-new-technique-manipulating-genes-holds-great-promisebut-rules-are-needed-govern-its]

9.     Cyronski D (2016) CRISPR gene-editing tested in a person for the first time. Nature News [Online: https://www.nature.com/news/crispr-gene-editing-tested-in-a-person-for-the-first-time-1.20988]

10.  Human Genome Editing: Science, Ethics, and Governance (2017) The National Academies of Sciences, Engineering and Medicine [Online: https://nationalacademies.org/gene-editing/consensus-study/index.htm]