Farewell, Big Steve

Steven Weinberg, a giant of theoretical physics, passed on July 23, 2021 -- he was 88 years old. His best known work, for which he received the Nobel prize, proposed the unification of electromagnetic and weak forces, and formed a key component of the Standard Model of particle physics. But his lifetime of work ranged from cosmology to gravitation to quantum field theory to foundations of quantum mechanics. A brief autobiography.

Wikipedia: It is a story widely told that Steven Weinberg, who inherited Schwinger's paneled office in Lyman Laboratory (Harvard Physics department), there found a pair of old shoes, with the implied message, "think you can fill these?"

Indeed, it is true that almost no one on the planet could have filled Schwinger's shoes. But Big Steve did, and more.

 

Below I've reproduced a post from 2017, Steven Weinberg: What's the matter with quantum mechanics? 

The video of Weinberg's talk is from 2016, when he would have been 83 or so.

In this public lecture Weinberg explains the problems with the two predominant interpretations of quantum mechanics, which he refers to as Instrumentalist (e.g., Copenhagen) and Realist (e.g., Many Worlds). The term "interpretation" may be misleading because what is ultimately at stake is the nature of physical reality. Both interpretations have serious problems, but the problem with Realism (in Weinberg's view, and my own) is not the quantum multiverse, but rather the origin of probability within deterministic Schrodinger evolution. Instrumentalism is, of course, ill-defined nutty mysticism 8-)

Physicists will probably want to watch this at 1.5x or 2x speed. The essential discussion is at roughly 22-40min, so it's only a 10 minute investment of your time. These slides explain in pictures.

See also Weinberg on Quantum Foundations, where I wrote:

It is a shame that very few working physicists, even theoreticians, have thought carefully and deeply about quantum foundations. Perhaps Weinberg's fine summary will stimulate greater awareness of this greatest of all unresolved problems in science.

and quoted Weinberg:

... today there is no interpretation of quantum mechanics that does not have serious flaws. 

Posts on this blog related to the Born Rule, etc., and two of my papers:

The measure problem in many worlds quantum mechanics

On the origin of probability in quantum mechanics

Dynamical theories of wavefunction collapse are necessarily non-linear generalizations of Schrodinger evolution, which lead to problems with locality.

Among those who take the Realist position seriously: Feynman and Gell-Mann, Schwinger, Hawking, and many more.

Embryo Screening for Polygenic Disease Risk: Recent Advances and Ethical Considerations (Genes 2021 Special Issue)

It is a great honor to co-author a paper with Simon Fishel, the last surviving member of the team that produced the first IVF baby (Louise Brown) in 1978. His mentors and collaborators were Robert Edwards (Nobel Prize 2010) and Patrick Steptoe (passed before 2010). In the photo above, of the very first scientific conference on In Vitro Fertilization (1981), Fishel (far right), Steptoe, and Edwards are in the first row. More on Simon and his experiences as a medical pioneer below. 

This article appears in a Special Issue: Application of Genomic Technology in Disease Outcome Prediction.

Embryo Screening for Polygenic Disease Risk: Recent Advances and Ethical Considerations 

L. Tellier, J. Eccles, L. Lello, N. Treff, S. Fishel, S. Hsu 

Genes 2021, 12(8), 1105 

https://doi.org/10.3390/genes12081105 

Machine learning methods applied to large genomic datasets (such as those used in GWAS) have led to the creation of polygenic risk scores (PRSs) that can be used identify individuals who are at highly elevated risk for important disease conditions, such as coronary artery disease (CAD), diabetes, hypertension, breast cancer, and many more. PRSs have been validated in large population groups across multiple continents and are under evaluation for widespread clinical use in adult health. It has been shown that PRSs can be used to identify which of two individuals is at a lower disease risk, even when these two individuals are siblings from a shared family environment. The relative risk reduction (RRR) from choosing an embryo with a lower PRS (with respect to one chosen at random) can be quantified by using these sibling results. New technology for precise embryo genotyping allows more sophisticated preimplantation ranking with better results than the current method of selection that is based on morphology. We review the advances described above and discuss related ethical considerations.

I excerpt from the paper below. 

Some related links: 

First Baby Born from a Polygenically Screened Embryo (video panel) 

Polygenic Embryo Screening: comments on Carmi et al. and Visscher et al.

Dalton Conley (Princeton) and collaborators find that 68% of surveyed Americans had positive attitudes concerning polygenic screening of embryos.

Introduction:

Over a million babies are born each year via IVF [1,2]. It is not uncommon for IVF parents to have more than one viable embryo from which to choose, as typical IVF cycles can produce four or five. The embryo that is transferred may become their child, while the others might not be used at all. We refer to this selection problem as the “embryo choice problem”. In the past, selections were made based on criteria such as morphology (i.e., rate of development, symmetry, general appearance) and chromosomal normality as determined by aneuploidy testing. 

Recently, large datasets of human genomes together with health and disease histories have become available to researchers in computational genomics [3]. Statistical methods from machine learning have allowed researchers to build risk predictors (e.g., for specific disease conditions or related quantitative traits, such as height or longevity) that use the genotype alone as input information. Combined with the precision genotyping of embryos, these advances provide significantly more information that can be used for embryo selection to IVF parents. 

In this brief article, we provide an overview of the advances in genotyping and computational genomics that have been applied to embryo selection. We also discuss related ethical issues, although a full discussion of these would require a much longer paper. ...

 Ethical considerations:

For further clarification, we explore a specific scenario involving breast cancer. It is well known that monogenic BRCA1 and BRCA2 variants predispose women to breast cancer, but this population is small—perhaps a few per thousand in the general population. The subset of women who do not carry a BRCA1 or BRCA2 risk variant but are at high polygenic risk is about ten times as large as the BRCA1/2 group. Thus, the majority of breast cancer can be traced to polygenic causes in comparison with commonly tested monogenic variants. 

For BRCA carrier families, preimplantation screening against BRCA is a standard (and largely uncontroversial) recommendation [39]. The new technologies discussed here allow a similar course of action for the much larger set of families with breast cancer history who are not carriers of BRCA1 or BRCA2. They can screen their embryos in favor of a daughter whose breast cancer PRS is in the normal range, avoiding a potentially much higher absolute risk of the condition. 

The main difference between monogenic BRCA screening and the new PRS screening against breast cancer is that the latter technology can help an order of magnitude more families. From an ethical perspective, it would be unconscionable to deny PRS screening to BRCA1/2-negative families with a history of breast cancer. ...

 

On Simon Fishel's experiences as an IVF pioneer (see here):

Today millions of babies are produced through IVF. In most developed countries roughly 3-5 percent of all births are through IVF, and in Denmark the fraction is about 10 percent! But when the technology was first introduced with the birth of Louise Brown in 1978, the pioneering scientists had to overcome significant resistance. There may be an alternate universe in which IVF was not allowed to develop, and those millions of children were never born. 

Wikipedia: ...During these controversial early years of IVF, Fishel and his colleagues received extensive opposition from critics both outside of and within the medical and scientific communities, including a civil writ for murder.[16] Fishel has since stated that "the whole establishment was outraged" by their early work and that people thought that he was "potentially a mad scientist".[17] 

I predict that within 5 years the use of polygenic risk scores will become common in some health systems (i.e., for adults) and in IVF. Reasonable people will wonder why the technology was ever controversial at all, just as in the case of IVF.

Figure below from our paper. EHS = Embryo Health Score. 

The History of the Planck Length and the Madness of Crowds

I had forgotten about the 2005-06 email correspondence reproduced below, but my collaborator Xavier Calmet reminded me of it today and I was able to find these messages.

The idea of a minimal length of order the Planck length, arising due to quantum gravity (i.e., quantum fluctuations in the structure of spacetime), is now widely accepted by theoretical physicists. But as Professor Mead (University of Minnesota, now retired) elaborates, based on his own experience, it was considered preposterous for a long time. 

Large groups of people can be wrong for long periods of time -- in financial markets, academia, even theoretical physics. 

Our paper, referred to by Mead, is 

Minimum Length from Quantum Mechanics and Classical General Relativity 

X. Calmet, M. Graesser, and S. Hsu  

https://arxiv.org/abs/hep-th/0405033  

Phys Rev Letters Vol. 93, 21101 (2004)

The related idea, first formulated by R. Buniy, A. Zee, and myself, that the structure of Hilbert Space itself is likely discrete (or "granular") at some fundamental level, is currently considered preposterous, but time will tell. 

More here. 

At bottom I include a relevant excerpt from correspondence with Freeman Dyson in 2005.

Dear Drs. Calmet, Graesser, Hsu,

I read with interest your article in Phys Rev Letters Vol. 93, 21101 (2004), and was pleasantly surprised to see my 1964 paper cited (second citation of your ref. 1).  Not many people have cited this paper, and I think it was pretty much forgotten the day it was published, & has remained so ever since.  To me, your paper shows again that, no matter how one looks at it, one runs into problems trying to measure a distance (or synchronize clocks) with greater accuracy than the Planck length (or time).

I feel rather gratified that the physics community, which back then considered the idea of the Planck length as a fundamental limitation to be quite preposterous, has since come around to (more or less) my opinion.  Obviously, I deserve ZERO credit for this, since I'm sure that the people who finally reached this conclusion, whoever they were, were unaware of my work.  To me, this is better than if they had been influenced by me, since it's good to know that the principles of physics lead to this conclusion, rather than the influence of an individual.  I hope that makes sense. ...

You might be amused by one story about how I finally got the (first) paper published after 5 years of referee problems.  A whole series of referees had claimed that my eq. (1), which is related to your eq. (1), could not be true.  I suspect that they just didn't want to read any further.  Nothing I could say would convince them, though I'm sure you would agree that the result is transparently obvious.  So I submitted another paper which consisted of nothing but a lengthy detailed proof of eq. (1), without mentioning the connection with the gravitation paper.  The referees of THAT paper rejected it on the grounds that the result was trivially obvious!!  When I pointed out this discrepancy to the editors, I got the gravitation paper reconsidered and eventually published.

But back then no one considered the Planck length to be a candidate as a fundamental limitation.  Well, almost no one.  I did receive support from Henry Primakoff, David Bohm, and Roger Penrose.  As far as I can recall, these were the only theoretical physicists of note who were willing to take this idea seriously (and I talked to many, in addition to reading the reports of all the referees).

Well anyway, I greet you, thank you for your paper and for the citation, and hope you haven't found this e-mail too boring.

Yours Sincerely,

C.  Alden  Mead

Dear Dr. Mead,

Thank you very much for your email message. It is fascinating to learn the history behind your work. We found your paper to be clearly written and useful.

Amusingly, we state at the beginning of our paper something like "it is widely believed..." that there is a fundamental Planck-length limit. I am sure your paper made a contribution to this change in attitude. The paper is not obscure as we were able to find it without much digging.

Your story about the vicissitudes of publishing rings true to me. I find such stories reassuring given the annoying obstacles we all face in trying to make our little contributions to science.

Finally, we intend to have a look at your second paper. Perhaps we will find another interesting application of your ideas.

Warm regards,

Stephen Hsu

Xavier Calmet

Michael Graesser

 

Dear Steve,

Many thanks for your kind reply.  I find the information quite interesting, though as you say it leaves some historical questions unanswered.  I think that Planck himself arrived at his length by purely dimensional considerations, and he supposedly considered this very important.

As you point out, it's physically very reasonable, perhaps more so in view of more recent developments.  It seemed physically reasonable to me back in 1959, but not to most of the mainstream theorists of the time.

I think that physical considerations (such as yours and mine) and mathematical ones should support and complement each other.  The Heisenberg-Bohr thought experiments tell us what a correct mathematical formalism should provide, and the formal quantum mechanics does this and, of course, much more.  Same with the principle of equivalence and general relativity.  Now, the physical ideas regarding the Planck length & time may serve as a guide in constructing a satisfactory formalism.  Perhaps string theory will prove to be the answer, but I must admit that I'm ignorant of all details of that theory.

Anyway, I'm delighted to correspond with all of you as much as you wish, but I emphasize that I don't want to be intrusive or become a nuisance.

As my wife has written you (her idea, not mine), your e-mail was a nice birthday present.

Kindest Regards, Alden

See also this letter from Mead which appeared in Physics Today.  

The following is from Freeman Dyson:

 ... to me the most interesting is the discrete Hilbert Space paper, especially your reference [2] proving that lengths cannot be measured with error smaller than the Planck length. I was unaware of this reference but I had reached the same conclusion independently.

 

Peter Shor on Quantum Factorization and Error Correction

 

This talk by Peter Shor describes the discovery of his quantum algorithm for prime factorization, and the discovery of quantum error correcting codes. The talk commemorates the first conference (Endicott House meeting) on the physics of computation in 1981. See 40 Years of Quantum Computation and Quantum Information.

Shor did not attend the 1981 meeting, where Feynman gave the keynote address Simulating Physics With Computers -- he was in his senior year at Caltech. But he recalls a talk that Feynman gave around the same time, on the possibility that negative probabilities might illuminate the EPR experiment and the Bell inequalities. 

Coincidentally, in my senior year (1986) I got Feynman to give a talk to the Society of Physics Students on this very topic! (I think I was president of SPS at the time.)

Winner Take All in Global E-Commerce? Alibaba vs Amazon

 

Alibaba and Amazon are set to fight it out for global e-commerce dominance. Both are building out distribution networks all over the world. It might not be winner take all, but there are huge returns to scale so there may be only a few winners that dominate in the future.

Alibaba has some big advantages: lower cost structure (PRC salaries) and better direct contacts with the factories in China that produce the goods. 

In fact, a major trend underway is disintermediation between manufacturers and consumers. See, e.g., Shein, with 100M+ downloads (fast fashion).

All of these companies form the C2M (consumer to manufacturer) layer that provides the following functions.

1. Fulfillment and inventory management

2. Product and price discovery 

3. Product evaluation, trust and consumer confidence

Item #1 has both physical and information infrastructure components, and is the most expensive to build. Items #2 and #3 can be built entirely virtually with much lower barrier to entry.

Just for fun I checked on AliExpress and I could find many of the same products as on Amazon, but at much lower prices. Not surprising, as it's all made in China these days.

At the moment Amazon delivery to US customers is much faster, but the situation varies by country and is changing rapidly.

Decline of the American Empire: Afghan edition (stay tuned for more)

There are photos and video to remind us of the ignominious US withdrawal from S. Vietnam after twenty years of conflict and millions of deaths.

Over the July 4th weekend, the US military abandoned Bagram airforce base in Afghanistan, without even informing the Afghan commander and his troops. 

Conveniently for our warmongering neocon "nation-building" interventionist elites, there are (as yet) no photos of this pullout.

BAGRAM, Afghanistan (AP) — The U.S. left Afghanistan’s Bagram Airfield after nearly 20 years by shutting off the electricity and slipping away in the night without notifying the base’s new Afghan commander, who discovered the Americans’ departure more than two hours after they left, Afghan military officials said. 

Afghanistan’s army showed off the sprawling air base Monday, providing a rare first glimpse of what had been the epicenter of America’s war to unseat the Taliban and hunt down the al-Qaida perpetrators of the 9/11 attacks on America. The U.S. announced Friday it had completely vacated its biggest airfield in the country in advance of a final withdrawal the Pentagon says will be completed by the end of August. 

“We (heard) some rumor that the Americans had left Bagram ... and finally by seven o’clock in the morning, we understood that it was confirmed that they had already left Bagram,” Gen. Mir Asadullah Kohistani, Bagram’s new commander said. ...

I wrote the following (2017) in Remarks on the Decline of American Empire:

1. US foreign policy over the last decades has been disastrous -- trillions of dollars and thousands of lives expended on Middle Eastern wars, culminating in utter defeat. This defeat is still not acknowledged among most of the media or what passes for intelligentsia in academia and policy circles, but defeat it is. Iran now exerts significant control over Iraq and a swath of land running from the Persian Gulf to the Mediterranean. None of the goals of our costly intervention have been achieved. We are exhausted morally, financially, and militarily, and still have not fully extricated ourselves from a useless morass. George W. Bush should go down in history as the worst US President of the modern era. 

2. We are fortunate that the fracking revolution may lead to US independence from Middle Eastern energy. But policy elites have to fully recognize this possibility and pivot our strategy to reflect the decreased importance of the region. The fracking revolution is a consequence of basic research from decades ago (including investment from the Department of Energy) and the work of private sector innovators and risk-takers. 

3. US budget deficits are a ticking time bomb, which cripple investment in basic infrastructure and also in research that creates strategically important new technologies like AI. US research spending has been roughly flat in inflation adjusted dollars over the last 20 years, declining as a fraction of GDP. 

4. Divisive identity politics and demographic trends in the US will continue to undermine political cohesion and overall effectiveness of our institutions. ("Civilizational decline," as one leading theoretical physicist observed to me recently, remarking on our current inability to take on big science projects.) 

5. The Chinese have almost entirely closed the technology gap with the West, and dominate important areas of manufacturing. It seems very likely that their economy will eventually become significantly larger than the US economy. This is the world that strategists have to prepare for. Wars involving religious fanatics in unimportant regions of the world should not distract us from a possible future conflict with a peer competitor that threatens to match or exceed our economic, technological, and even military capability.

If you are young and naive and still believe that we can mostly trust our media and government, watch these videos for a dose of reality.

[ The video embedded above was a documentary about Julian Assange and Wikileaks on the DW channel, which I had queued to show the Collateral Murder video. It included an interview with the US soldier who saved one of the children in the rescue van that was hit with 30mm Apache fire. Inexplicably, DW has now removed the video from their channel. Click through to YouTube below for the content. ]

Some things never change. Recall the personal sacrifices made by people like Daniel Ellsberg to reveal the truth about the Vietnam war. Today it is Julian Assange...

Note Added: While it was easy to predict this outcome in 2017, it wasn't much harder to call it in 2011. See this piece from The Onion:

KABUL, AFGHANISTAN—In what officials said was the "only way" to move on from what has become a "sad and unpleasant" situation, all 100,000 U.S. military and intelligence personnel crept out of their barracks in the dead of night Sunday and quietly slipped out of Afghanistan. 

U.S. commanders explained their sudden pullout in a short, handwritten note left behind at Bagram Airfield, their largest base of operations in the country. 

"By the time you read this, we will be gone," the note to the nation of Afghanistan read in part. "We regret any pain this may cause you, but this was something we needed to do. We couldn't go on like this forever." 

"We still care about you very much, but, in the end, we feel this is for the best," the note continued. "Please, just know that we are truly sorry and that we wish you all the greatest of happiness in the future." 

... After reportedly taking a "long look in the mirror" last week, senior defense officials came to the conclusion that they had "wasted a decade of [their] lives" with Afghanistan ...

Polygenic Embryo Screening: comments on Carmi et al. and Visscher et al.

In this post I discuss some recent papers on disease risk reduction from polygenic screening of embryos in IVF (PGT-P). I will focus on the science but at the end will include some remarks about practical and ethical issues. 

The two papers are 

Carmi et al. 

https://www.biorxiv.org/content/10.1101/2020.11.05.370478v3 

Visscher et al. 

https://www.nejm.org/doi/full/10.1056/NEJMsr2105065

Both papers study risk reduction in the following scenario: you have N embryos to choose from, and polygenic risk scores (PRS) for each which have been computed from SNP genotype. Both papers use simulated data -- they build synthetic child (embryo) genotypes in order to calculate expected risk reduction. 

I am very happy to see serious researchers like Carmi et al. and Visscher et al. working on this important topic. 

Here are some example results from the papers: 

Carmi et al. find a ~50% risk reduction for schizophrenia from selecting the lowest risk embryo from a set of 5. For a selection among 2 embryos the risk reduction is ~30%. (We obtain a very similar result using empirical data: real adult siblings with known phenotype.)

Visscher et al. find the following results, see Table 1 and Figure 2 in their paper. To their credit they compute results for a range of ancestries (European, E. Asian, African). We have performed similar calculations using siblings but have not yet published the results for all ancestries.

Relative Risk Reduction (RRR): 

Hypertension: 9-18% (ranges depend on specific ancestry) 

Type 2 Diabetes: 7-16% 

Coronary Artery Disease: 8-17% 

Absolute Risk Reduction (ARR): 

Hypertension: 4-8.5% (ranges depend on specific ancestry) 

Type 2 Diabetes: 2.6-5.5% 

Coronary Artery Disease: 0.55-1.1%

Note, families with a history of the disease would benefit much more than this. For example, parents with a family history of breast cancer or heart disease or schizophrenia will often produce some embryos with very high PRS and others in the normal range. Their absolute risk reduction from selection is many times larger than the population average results shown above. 

My research group has already published work in this area using data from actual siblings: tens of thousands of individuals who are late in life (e.g., 50-70 years old), for whom we have health records and genotypes. 

See Sibling Validation of Polygenic Risk Scores and Complex Trait Prediction (blog post) and https://www.nature.com/articles/s41598-020-69927-7 (paper).

We have shown that polygenic risk predictors can identify, using genotype alone, which sibling in a pair has a specific disease condition: the sib with high PRS is much more likely to have the condition than the sib with normal range PRS. In those papers we also computed Relative Risk Reduction (RRR), which is directly relevant to embryo selection. Needless to say I think real sib data provides better validation of PRS than simulated genotypes. The adult sibs have typically experienced a shared family environment and also exhibit negligible population stratification relative to each other. Using real sib data reduces significantly some important confounds in PRS validation. 

See also these papers: Treff et al. [1] [2] [3]

Here are example results from our work on absolute and relative risk reduction. (Selection from 2 embryos.)

Regarding pleiotropy (discussed in the NEJM article), the Treff et al. results linked above show that selection using a Genomic Index, which is an aggregate of several polygenic risk scores, simultaneously reduces risks across all of the ~12 disease conditions in the polygenic disease panel. That is, risk reduction is not zero-sum, as far as we can tell: you are not forced to trade off one disease risk against another, at least for the 12 diseases on the panel. Further work on this is in progress. 

In related work we showed that DNA regions used to predict different risks are largely disjoint, which also supports this conclusion. See 

Pleiotropy: Myths and Reality (blog post) 

https://www.nature.com/articles/s41598-020-68881-8 (paper).

To summarize, several groups have now validated the risk reduction from polygenic screening (PGT-P). The methodologies are different (i.e., simulated genotypes vs studies using large numbers of adult siblings) but come to similar conclusions. 

Whether one should regard, for example, relative and absolute risk reduction in type 2 diabetes (T2D) of ~40% and ~3% (from figure above) as important or valuable is a matter of judgement. 

Studies suggest that type 2 diabetes results in an average loss of over 10 quality-adjusted life years -- i.e., more than a decade. So reducing an individual's risk of T2D by even a few percent seems significant to me. 

Now multiply that by a large factor, because selection using a genomic index (see figure) produces simultaneous risk reductions across a dozen important diseases.

Finally, polygenic predictors are improving rapidly as more genomic and health record data become available for machine learning. All of the power of modern AI technology will be applied to this data, and risk reductions from selection (PGT-P) will increase significantly over time. See this 2021 review article for more.

Practical Issues 

Aurea, the first polygenically screened baby (PGT-P), was born in May 2020.

See this panel discussion, which includes 

Dr. Simon Fishel (member of the team that produced the first IVF baby) 

Elizabeth Carr (first US IVF baby) 

Prof. Julian Savalescu (Uehiro Chair in Practical Ethics at the University of Oxford) 

Dr. Nathan Treff (Chief Scientist, Genomic Prediction)

Dr. Rafal Smigrodzki (MD PhD, father of Aurea) 

Astral Codex Ten recently posted on this topic: Welcome Polygenically Screened Babies :-) Many of the comments there are of high quality and worth reading. 

Ethical Issues 

Once the basic scientific results are established, one can meaningfully examine the many ethical issues surrounding embryo selection. 

My view has always been that new genomic technologies are so powerful that they should be widely understood and discussed -- by all of society, not just by scientists. 

However, to me it is clear that the potential benefits of embryo PRS screening (PGT-P) are very positive and that this technology will eventually be universally adopted. 

Today millions of babies are produced through IVF. In most developed countries roughly 3-5 percent of all births are through IVF, and in Denmark the fraction is about 10 percent! But when the technology was first introduced with the birth of Louise Brown in 1978, the pioneering scientists had to overcome significant resistance. There may be an alternate universe in which IVF was not allowed to develop, and those millions of children were never born.

Wikipedia: ...During these controversial early years of IVF, Fishel and his colleagues received extensive opposition from critics both outside of and within the medical and scientific communities, including a civil writ for murder.[16] Fishel has since stated that "the whole establishment was outraged" by their early work and that people thought that he was "potentially a mad scientist".[17]

I predict that within 5 years the use of polygenic risk scores will become common in some health systems (i.e., for adults) and in IVF. Reasonable people will wonder why the technology was ever controversial at all, just as in the case of IVF.

This is a very complex topic. For an in-depth discussion I refer you to this recent paper by Munday and Savalescu. Savalescu, Uehiro Chair in Practical Ethics at the University of Oxford, is perhaps the leading philosopher / bioethicist working in this area. 

Three models for the regulation of polygenic scores in reproduction 

Journal of Medical Ethics

The past few years have brought significant breakthroughs in understanding human genetics. This knowledge has been used to develop ‘polygenic scores’ (or ‘polygenic risk scores’) which provide probabilistic information about the development of polygenic conditions such as diabetes or schizophrenia. They are already being used in reproduction to select for embryos at lower risk of developing disease. Currently, the use of polygenic scores for embryo selection is subject to existing regulations concerning embryo testing and selection. Existing regulatory approaches include ‘disease-based' models which limit embryo selection to avoiding disease characteristics (employed in various formats in Australia, the UK, Italy, Switzerland and France, among others), and 'laissez-faire' or 'libertarian' models, under which embryo testing and selection remain unregulated (as in the USA). We introduce a novel 'Welfarist Model' which limits embryo selection according to the impact of the predicted trait on well-being. We compare the strengths and weaknesses of each model as a way of regulating polygenic scores. Polygenic scores create the potential for existing embryo selection technologies to be used to select for a wider range of predicted genetically influenced characteristics including continuous traits. Indeed, polygenic scores exist to predict future intelligence, and there have been suggestions that they will be used to make predictions within the normal range in the USA in embryo selection. We examine how these three models would apply to the prediction of non-disease traits such as intelligence. The genetics of intelligence remains controversial both scientifically and ethically. This paper does not attempt to resolve these issues. However, as with many biomedical advances, an effective regulatory regime must be in place as soon as the technology is available. If there is no regulation in place, then the market effectively decides ethical issues.

Dalton Conley (Princeton) and collaborators find that 68% of surveyed Americans had positive attitudes concerning polygenic screening of embryos.