Sunday, November 10, 2019

Good and Bad Journalism on Embryo Screening: The Economist vs Science Magazine

Modern genetics will improve health and usher in “designer” children (Economist), which I linked to in the last post, does an excellent job of covering the scientific, technical, and ethical issues raised by recent advances in polygenic risk prediction and embryo screening.

The author, Ananyo Bhattacharya, is an experienced science writer with (if I recall correctly) a degree in Physics. His forthcoming book is an ambitious scientific / intellectual history of John von Neumann!

What did Ananyo get right in his article?

1. He gives an overview of polygenic risk scores (PRS) and the underlying science behind GWAS studies and construction of risk predictors
2. He describes how PRS will have important applications in health care as well as in IVF
3. He discusses the important ethical and societal aspects of embryo screening

As someone who works in this area, I can say that I don't know of any popular work that combines the clarity, precision, and concision of this article (3 pages).

Unfortunately, not all journalism reaches this high standard.

For example, a really terrible ("click-bait") article appeared in the News section of Science recently, which conflated embryo screening to reduce disease risk with the optimization of complex traits such as IQ or height. I had numerous email exchanges with the writer (a self-described "non-scientist"), running to thousands of words, and including references to published work on disease risk reduction from genomic prediction. The resulting story was irresponsible, and very confusing to readers. I can judge this directly and empirically from communications I received in reaction to it.

Here is the letter we submitted to Science in response to the article. We do not know whether our letter will be published, but the News editor has already made significant revisions to the original article in response to our complaints.
Dear Editor,

Your news article Screening embryos for IQ and other complex traits is premature, study concludes (Oct 24 2019) contained significant errors, which we correct below. 
Each year roughly 2 million IVF embryos are genetically screened worldwide. In many developed countries, a significant fraction of all babies are born via IVF (e.g., almost 10% in Denmark). Reproductive health and IVF are serious matters and deserve serious journalism, not the inaccurate sensationalism of your article. Errors persist in the article even after numerous email exchanges (consisting of thousands of words of text, including references to published research) with your writer, informing your journalist clearly of these misrepresentations.

1. Your article failed to cite published work that shows significant risk reduction for complex disease conditions using polygenic predictors to select between sibling embryos. These results, which we emphasized many times to the writer, explicitly contradict this entire paragraph of the article:

The work "is the first to empirically test the viability of screening embryos" for traits that are influenced by many genes, says sociologist and demographer Melinda Mills of the University of Oxford in the United Kingdom. Such embryo screening goes beyond today's testing for single-gene disorders and currently "isn't plausible," she concludes.

[ Note: this paragraph has been altered now in the Science article. The original is given above. Science added this to the modified article, but still without referencing our work: *Clarification, 5 November, 10:05 a.m.: This story has been updated to clarify the context of a quote from Melinda Mills to emphasize that she was referring to screening for desirable traits, not disease risks. ]

Carmi et al. is not the first to empirically test embryo screening. Our published work predates it. Furthermore, Carmi’s work uses far less sibling data than our preceding work - an order of magnitude fewer siblings, 2-3 orders of magnitude fewer families (28 vs several thousand). Carmi’s analysis relies primarily on “simulated” data, ours is 100% empirical. We made your writer abundantly aware of the published work validating differentiation of real siblings (not “synthetic genomes”) by polygenic disease status, linking to it in email correspondence:

“You would be negligent to cite a BioRxiv preprint without thoroughly addressing our peer-reviewed, formally published work in the field, significantly predating this preprint.”

Your article misleads the reader to think that the dozens of IVF clinics and laboratories working with Genomic Prediction to screen embryos for complex (polygenic) disease risk do so without detailed, published validation. This is an irresponsible, unprofessional, and dangerous misrepresentation. We reserve the right to seek damages.

2. The article, and especially the title of the article, conflates screening embryos for disease with optimizing embryos for IQ, and gives the false impression that Carmi address the use-case of our patients: relative risk reduction of disease. This is misleading, as we repeatedly emphasized in writing with your journalist: “You will misrepresent our test if you fail to make this distinction...” , etc. The reader is misled by the article - especially the headline - to think that Carmi’s work addresses the current polygenic use-case of screening embryos for relative risk reduction of disease, rather than Carmi’s futuristic thought experiment of IQ optimization. This conflation is irresponsible, and a disservice to everyone, particularly to the IVF families using screening to reduce polygenic disease risk.

From IVF scientific pioneer Prof. Simon Fishel, external to Genomic Prediction. Fishel is former Deputy Scientific Director of the world's first IVF clinic, which included Nobel prize winning colleagues Dr. Steptoe and Dr. Edwards. His response to the Science article: "IVF itself was a revolutionary new technology that also endured an initial response of similar misrepresentation. There is no reason to repeat the mistakes of the past; Science should aim to convey the state of the field with less inaccuracy."

We ask that you publish this letter, and publish a correction to the article. We also ask that you recommit yourself to serious science reporting.


Prof. Stephen Hsu
Dr. Nathan Treff
Laurent C. A. Melchior Tellier
Dr. Jia Xu
Prof. Simon Fishel
Note, I commented on Carmi et al. when it first appeared, here. This commentary was one of the first things I shared with the journalist and it makes very clear the difference between optimization of traits such as height or IQ (which Genomic Prediction does not do) and disease risk reduction (which is the main focus of our report).

The following is from an email I sent to the writer and editors:
... disease conditions are themselves complex traits and are typically referred to as such, so the risk of confusion is high. From the Wikipedia article on Complex Traits: "Examples of complex traits include height, circadian rhythms, enzyme kinetics, and many diseases including diabetes and Parkinson's disease." ...
Hence the title of the Science article Screening embryos for IQ and other complex traits is premature, study concludes is extremely misleading.

The most important scientific point: we have demonstrated that polygenic predictors can differentiate between two adult siblings, one with the disease and the other without. This is the gold standard validation relevant for embryo selection -- the predictor can identify from DNA alone the sibling with higher risk of the disease. The evidence is very strong that we can reduce disease risk through embryo screening, and IVF parents have a right to make use of this capability.

In an era of rapid scientific progress and technological change, the public deserves careful, accurate reporting -- not sensationalism.

For future reference, here are simple sentences which a journalist can include in any future article on this topic:
Published validation studies, using genomic data from thousands of families, have shown that polygenic scores can predict which of two adult siblings has the disease, and which one is healthy. It is reasonable to conclude that these predictors can reduce disease risk through IVF embryo screening.

Thursday, November 07, 2019

The Economist on Polygenic Risk Scores and Embryo Selection

The graph at bottom says it all.

What is it worth to know that you, or your child, or your embryo, are in the top or bottom risk group for a broad array of common diseases?
Economist: Sometime next year, if all goes to plan, a gay male couple in California will have a child. The child in question will have been conceived by in vitro fertilisation. In this case a group of eggs from a female donor are now being fertilised by sperm from both fathers (half from one, half from the other). Of the resulting embryos, the couple will choose one to be implanted in a surrogate mother. An uplifting tale of the times, then, but hardly a newsworthy event. Except that it is.

Where the story becomes newsworthy is around the word “choose”. For the parents, in conjunction with a firm called Genomic Prediction, will pick the lucky embryo based on a genetically estimated risk of disease. Such pre-implantation testing is already used in some places, in cases where there is a chance of parents passing on a condition, such as Tay-Sachs disease, that is caused by a single faulty gene. Genomic Prediction is, however, offering something more wide-ranging. It is screening embryos for almost 1m single-nucleotide polymorphisms (snps). These are places where individual genomes routinely differ from one another at the level of an individual genetic letter. Individual snp differences between people rarely have much effect. But add them up and they can raise or lower by quite a lot the likelihood of someone suffering a particular disease. Generate several embryos and snp-test them, then, and you can pick out those that you think will grow up to be the healthiest. ...
See also this Economist podcast interview with the author of the article, who is also working on a book about John von Neumann!

Wednesday, November 06, 2019

Blade Runner November 2019

Blade Runner (1982) was set in November 2019.

Yes, progress has been a bit slow.

Blade Runner got one thing very right -- the two most important technologies of this century are AI and Genetic Engineering.

Where is the AI in Blade Runner, you ask? Not evident until Blade Runner 2049? Alien and Blade Runner take place in the same universe. A universe which contains the AI David as well as the engineered Replicants:

... a special feature on the Prometheus Blu-ray release makes the film even more interesting by tying it into the Blade Runner universe. Included as an entry in the journal of Peter Weyland (Guy Pearce), who in the film was obsessed with creating artificial life, is the following gem:
A mentor and long-departed competitor once told me that it was time to put away childish things and abandon my “toys.” He encouraged me to come work for him and together we would take over the world and become the new Gods. That’s how he ran his corporation, like a God on top of a pyramid overlooking a city of angels. Of course, he chose to replicate the power of creation in an unoriginal way, by simply copying God. And look how that turned out for the poor bastard. Literally blew up in the old man’s face. I always suggested he stick with simple robotics instead of those genetic abominations he enslaved and sold off-world, although his idea to implant them with false memories was, well… “amusing,” is how I would put it politely.
The mentor is Eldon Tyrell (Blade Runner), of course. See also here and the Tyrell-Weyland Connection.

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