The End of Sex and the Future of Human Reproduction

by Greely

“Will the future confront us with human GMOs? Greely provocatively declares yes, and, while clearly explaining the science, spells out the ethical, political, and practical ramifications.”―Paul Berg, Nobel Laureate and recipient of the National Medal of Science

Within twenty, maybe forty, years most people in developed countries will stop having sex for the purpose of reproduction. Instead, prospective parents will be told as much as they wish to know about the genetic makeup of dozens of embryos, and they will pick one or two for implantation, gestation, and birth. And it will be safe, lawful, and free. In this work of prophetic scholarship, Henry T. Greely explains the revolutionary biological technologies that make this future a seeming inevitability and sets out the deep ethical and legal challenges humanity faces as a result.

“Readers looking for a more in-depth analysis of human genome modifications and reproductive technologies and their legal and ethical implications should strongly consider picking up Greely’s The End of Sex and the Future of Human Reproduction … [It has] the potential to empower readers to make informed decisions about the implementation of advancements in genetics technologies.”
―Dov Greenbaum, Science

“[Greely] provides an extraordinarily sophisticated analysis of the practical, political, legal, and ethical implications of the new world of human reproduction. His book is a model of highly informed, rigorous, thought-provoking speculation about an immensely important topic.”
―Glenn C. Altschuler, Psychology Today

Genres: Science, Nonfiction, Biology, Genetics, Futurism, Gender and Sexuality

400 pages, Paperback

Published April 9, 2018

Reviews

[Christoph Weber · Rating 5 out of 5]

I've read my share of science books, and this is among the best. Greely writes clearly and explains complex concepts in a way that most laypeople can follow. As a bonus, he'll make you laugh from time to time.

Greely has thoroughly thought through (say that five times fast) the implications of "artificial" gamete production and cheap whole genome sequencing. If this future of "Easy PGD" plays out, it will be a fascinating one. Barring regulation, we will be able to eliminate genetic diseases (yes!); gay and lesbian couples will be able to have their own biological children (thumbs up!); so will geriatric women (that seems okay?); so will deceased individuals (hmm); close relatives will be able to have healthy children together (still weird, Jaime Lannister); and a single person will be able to have offspring as a "uniparent" (WTF). This is just a sampling of the intriguing possibilities Greely suggests lie in our near future. As a science fiction writer, this book is a gold mine.

I don't know how the future will play out, but I'll probably invest in genomics technologies, and I'll certainly recommend this book.

[Sam · Rating 4 out of 5]

Explains the astronomically complicated biological process that sperm and egg go through to create a human; it's a miracle any of us get born at all.

This book is a verbose but interesting way to learn about current medical reproductive technology like IVF & genetic disease screening.
The meat of it goes on to describe how exciting advancements in stem cell biology and genomics will change reproduction's role in society by allowing same sex couples to have biological children, eradicating genetic diseases, and turning the limited supply of eggs women are born with unlimited.

[Will · Rating 4 out of 5]

Some thoughts and quotes in a disorganized jumble:

Thesis of book: "sometime in the next 20-40 yrs, among humans with good health coverage,...children will be conceived in clinics. Eggs and sperm will be united through IVF...sequenced and carefully analyzed before ...transfer...safe legal and, to the prospective parents, free""

He has a really solid short section on genetics, infertility, the history of IVF and prenatal screening. Lucid prose, some funny lines, and he successfully avoids the pitfall that many non-fiction writers fall into: overhyping stuff that turns out to be BS

For someone who only develop an interest in science late in life, he does a really great job explaining meiosis, recombination, and the messy miracle of pregnancy.

A few representative quotes:
1. "DNA may seem like a finely engineered machine, but, in fact, it is more like your grandmother's attic, with occasional treasures half-hidden in the mass of useless clutter. "
2. on eggs and sperm size difference: "think of a small pea going into a basketball" (8)
3. regarding: IVF in rabbits "IVF had finally been achieved but, unfortunately, only in a species not generally thought to have infertility problems.""
4. on junk DNA prob not =junk DNA --> "Careful researchers and commentators, on the other hand, might call it 'junk' DNA""

In an example of mostly calling it right, which I applaud 👏 for a non-scientist, he is sober about the possibility of transgenerational epigenetics-- one of the few pop science writers who didn't get overhyped about it in the late 2010's...

A strength in this section is the combination of [history of science] + [practical implications]: he does a great job showing the progression of diff reproductive technologies, different methods of testing for genetic abnormalities, etc.

Quotes from history of science section:

1. "Human IVF may be the most important medical advance of the 20th century to have taken place without substantial support, financial or otherwise, from either corporations or governments...brought to life millions of people"
2. on the lack of correlation between embryo appearance and success of implantation: "One clear reality is that some of the best-looking embryos do not lead to pregnancies, while, on occasion, very low-grade embryos become healthy children"

Another strength is that he clearly explains, in non-scientific writing, important biases that research may have. Most pop science writers struggle with this aspect of science-- understanding the limitations of research, having a good outside perspective.

Example:
1. "in IVF pregnancies, the ectopic pregnancy rate is between 2 and 5 percent. (This may not be the result of the IVF process itself, as damage to the fallopian tubes that can cause ectopic pregnancies is also associated with fertility problems...women who need IVF to get pregnant may just be, on average, at higher risk for an ectopic pregnancy. )""Just want to highlight he clearly /gets/ an important uncertainty in the research here.

Some minor critique for first part:
1. I think he could have added a half-page or so of explanation of GWAS, which is alluded to in passing. If this gets addressed in later parts of book, then my critique is moot.
2. his section on SNP's being used in studies (around page 77) is a bit confusing: "SNP chips have pointed to many regions that are statistically associated with particular traits-- but too many regions and each associated with the trait only to a very small extent.
Perhaps he's criticizing the tiny effect sizes of each individual SNP variant and the very large # of SNP variants that contribute to complex traits? If so, it's sort of in line with much of med genetics thinking in that time, but aged poorly in time of GWAS

Bonus analogy he made that I liked! --> slime mold and human muscle! Multi-nucleated but with indistinct borders.

So far, very clear and enjoyable prose style. Excited to read the rest of the book...

Part 2 is careful futurism: what tech needs to get ironed out for Easy PGD? who would be motivated to produce that technology? where would the funding come from? etc.

though he doesn't quite put it that way, he points out what the rate-limiting step of Current PGD is: *egg retrieval* -->which is cumbersome, retrieves only a few eggs at a time, and comes with minor but real risk
- "as long as PGD requires egg retrieval, it will remain an uncommon procedure." (121)

He runs through 4 diff tech options that could circumvent this step:
1. in-vitro ripening of oocytes form Ovarian Slices
2. eggs from hESC's
3. eggs from iPSCs
4. eggs from cloned embryos

Quotes:
1. "If a doctor removed 5 percent of one ovary-- a slice about 1 cm high, 1 cm long, and .5 cm wide-- it should contain about 3,500 ovarian follicles, enough to make lots of embryos....in theory this small slice could provide enough eggs for seventy attempts at IVF" (122)

2. [gametogenesis research will be] "pushed forward by the desire for a way to make all kinds of human cells for research and for cell replacement therapy. " (130)

IOW, gametogenesis will be a spandrel of other stem cell research

There's an interesting analogy to non-disease trait research in genetics: seems like there's less funding for it + much of the work relies on data collected for other purposes. Likely why easily gathered phenotypes like [edu attainment] predominate:
"traits of potentially greatest interest, such as personality traits or cognitive skills, getting good data may prove hard" (141)

There's a solid section on the potential economics of Easy PGD which is too long to replicate here: suffice to say, even with conservative assumptions, a method of safe in-vitro gametogenesis would have a large market
I do quibble with some of his points on insurance and healthcare prices: laser eye surgery is a classic example of free-ish (not covered by insurance) market healthcare getting cheaper and better over the decades, in contrast to much of medicine! so its a weird example to choose.


"The large and very profitable fertility clinic industry is quite likely to see Easy PGD as a way to become even larger and more profitable." More customers, all other things being equal, does sound good for IVF docs, but:
IF in-vitro gametogenesis can manage to substitute egg retrieval with [skin biopsy + lab technicians working their magic], shouldn't that threaten IVF docs, since egg retrieval is a big part of services? Though they'd still be needed for embryo transfer so it is hard to know how that will all play out.

Moving on from the economic and technical arguments, he then delves into the legal and regulatory framework that might emerge around Easy PGD. Again, he mixes history with current regulation, which is a neat way to explain things .

Interesting facts:

1. I was surprised to learn that Europe is far more regulated in the ART space than the US: various countries have marriage requirements, limits on # of embryos to be transferred, # of cycles, lower age limits, and restrictions on non-heterosexual couples
2. What might account for the US's freer approach? a more pro-natalist culture, more libertarian society, and an "unwillingness to take no for an answer, especially from medicine" (169)
"Some countries have histories or cultures that make them ...skittish about human biotechnologies. Germany, with its Nazi legacy, is the prime example....Western Europe is a lot more concerned about genetic interventions, particularly in food, than the United States." (177)

He explains the uncertain role of the FDA in regulating Easy PGD, and suspects that gametogenesis would first have to be approved as a treatment for infertility before being used off-label for Easy PGD

"Under current law, at least, 'Easy PGD' will not require FDA approval. It is a...set of procedures and that is not what the FDA regulates...some of the sequencing methods will require FDA-reviewed devices, ...derived gametes used in Easy PGD will most likely have to be approved"

He thinks they'll be quite cautious about making stem cell derived babies, but points out the difficulties inherent in regulating non-medical uses of genomic information for embryo selection
"thanks to whole genome sequencing, Easy PGD will yield all the genetic information about prospective parents' embryos....who can say whether parents are making a decision based on medical risks, on nondisease traits, or (most likely) on some combination of these two" (171)


He has some suggestions on preventing non-consensual parenthood: " probably want to focus enforcement of this ban on those facilities that could transform cells into iPSCs and then into gametes by requiring that they have good evidence of consent to genetic parenthood..." (297)


The section on possible regulatory challenges to regulating Easy PGD is likely the most unique aspect of this book, and I'm not aware of anybody else with in-depth knowledge of the FDA who has written on it, so this is worth price of admission alone.

There's also a section on ethical objections to Easy PGD and responsa to those, which is quite good, but they're harder to summarize and I've encountered them before.

Hadn't encountered the following argument, though:
if 'nature' is taken more broadly than just its human aspect, Easy PGD is not particularly unnatural ...'nature'...provides many forms of reproduction....some species make thousands or even millions of offspring...some... practice infanticide or fratricide" (278)
which is a nice counter to the "it's unnatural" argument against Easy PGD.

I did appreciate his brief reference to Derek Parfit and some of the eccentricities of Lee Kwan Yew (1st PM of Singapore , Positive Eugenics "Love Boat" fame). There are some amusing references buried in this book

Overall, a great read for any general readers interested in this issue, practitioners in adjacent fields (REI, urology), and science-minded folks who want a sense of the legal/regulatory challenges that might arise.

Not the book for anybody who wants far-future extrapolations of a biological Singularity 🚀🚀 or what the societal impact of multiple generations of embryo selection for traits could be-- the book stays focused on 20-40 yrs in the future...

[jojo · Rating 4 out of 5]

4 ⭐️ this was really interesting book over reproductive history and what the future looks like also made me think of gattaca

[Sara · Rating 3 out of 5]

Ohhh this book had Such promise. But you know a book is too long when the author says ‘this book is already too long’.

On the plus side: the idea of induced stem cells leaving to reproductive cells as a way to change society and end infertility is extremely fascinating !! I think I flew through the first few chapters like ‘woah! This is so cool’

On the bad side, the author gets sooooo bogged down by legalese and politics that the book absolutely drags in the middle. It gets back on its feet a bit at the end when it delves into morality.

It’s ... kind of a shame that the author already seemingly knew the book’s flaws going in and didn’t quite know how to edit it to be more concise. Still if you can maybe skim through the middle and hit the main points (the enormous potential ! Will it help or harm society? Is it inevitable?) I think it’s such a great topic to explore.

[Bobby Warshaw · Rating 5 out of 5]

I thoroughly enjoyed this book. It speaks to the very basic building block of humanity, a topic I was surprised to realize how little I knew about, and how glad I am to now know more.

The book breaks into two parts. First, it's a basic discussion on the science behind human reproduction. Second, it breaks down the likely future of reproduction based on scientific and societal development. The author does an excellent job of breaking down concept ideas into very simple and understandable terms, while also maintaining a conversational and interesting voice.

[Joseph Carrabis · Rating 1 out of 5]

This may be a good book for...hmm...I'm really not sure. I accept the author's scholarship and I did think it was far too narrow a topic to fill 315 pages (hardcover edition). I also found his arguments repetitive.
So while this may be a good book for people who are curious about or want PGD (preimplantation genetic diagnosis), it is both too much of it and not enough of around it to for me to label it a worthy read.

[Antonio Gallo · Rating 4 out of 5]

Ogni giorno che passa sembra che il futuro si realizzi più come "fiction" che come realtà. Non si sa più se la letteratura insegue la vita o è la vita che si fa letteratura. Quello che un tempo si pensava fosse fantascienza, diventa non attuale, bensì addirittura obsoleto.

Da un minimo di 20 ad un massimo di 40 anni, la maggior parte delle persone non ricorrerà più al rapporto sessuale per concepire i propri figli. Ovuli e spermatozoi saranno uniti tramite la fecondazione in vitro. Il DNA degli embrioni così generati sarà poi sequenziato e scrupolosamente analizzato.

Pensiamo subito alla distopia di Aldous Huxley, Il Mondo Nuovo, quel libro che io, dinosauro digitale contemporaneo, leggevo e non capivo nella biblioteca di mio padre. Lui lo comprò negli trenta, quando era giovane, in quel piccolo paese di provincia merdionale italiana. Non so cosa abbia capito a quel tempo. Cercai di leggerlo anche io, ero poco più che un decenne. Non capii assolutamente nulla.

Me lo ritrovai tra gli studi di quella lingua inglese che poi mi ha introdotto nella realtà del mondo contemporaneo. Il Mondo Nuovo di Huxley inizia proprio all'interno di quel laboratorio di cui parla l'autore di questo libro. Ma non è un romanziere. E' uno degli scienziati e studiosi più importante del pianeta: Henry T. Greely, professore non solo di legge ma anche di genetica a Standford dove dirige il Center for Law and the Biosciences.

Un luminare che non scrive di avventure fantascientifiche, bensì di fatti. Nel suo libro egli sostiene che oggi già molti milioni di bambini sono nati senza essere stati concepiti con rapporti sessuali, ma grazie a fecondazioni in vitro o inseminazione.

Gli uomini stanno per mettere le loro mani sul segreto della vita. Non è un argomento semplice, nè tanto meno nuovo, ma sempre pericoloso. C'è il rischio di far saltare tutti i principi di un mondo, anzi di tanti mondi, sui quali si sono succedute le civiltà su questo pianeta.

Niente di nuovo sotto il sole. Potrei consolarmi dicendo, ancora una volta che lo ha detto Qoelet oltre duemila anni orsono. Ma questa volta credo che si tratti di una sfida mai fatta prima nella storia dell'umanità. Una lunga serie di questioni morali vengono messe sul piatto della vita in termini di sicurezza, correttezza, di coercizione e di struttura non solo della società e della famiglia, come della naturalità e della volonta di Dio, un dio comunque ce lo configuriamo.

Saranno inevitabili le divisioni, le discussioni di immoralità, violenza, libertà e quant'altro fa parte della nostra storia di uomini. Ci sono molte somiglianze con il mondo immaginato dallo scrittore inglese Huxley, come anche molte differemze. Lo scrittore e scienziato Greely non ne fa una questione morale. Nel suo libro fa semplicemente delle previsioni. Egli fornisce idee e informazioni per affrontare il futuro.

Come del resto aveva già fatto Huxley, non come scienziato ma come romanziere. Qui non si tratta di parlare di un futuro immagianario come quello che possono creare i romanzieri che scrivono con l'aiuto della loro fantasia ed intelligenza. Qui si tratta di pensare a come vorremo che sarà la nostra società imminente. Insomma il futuro che ci aspetta. E questo ce lo dovremo costruire noi. Questo libro ci offre un percorso ed una riflessione.

[Matea · Rating 5 out of 5]

Slightly repetitive but if you can manage that and the length, the breadth of the issues covered that arise with this future means of human reproduction (PGD, or preimplantation genetic diagnosis) are worth the read.
The introduction to the scientific basics of the new technology is coherent and well-written. The author’s study of the legal and political aspects of introducing PGD were an interesting addition especially knowing that he probably knows what he’s talking about (Greely is law prof at Stanford and a part of several boards and committees regarding bioethics, including the California Advisory Committee on Human Stem Cell Research).

[Katherine Bassil · Rating 5 out of 5]

An enlightening, informative, and thought-provoking book. The author provides valuable information and an overview of human reproductive technologies all while stimulating the reader to think for themselves and have their own opinion on the topic. Even though I do not agree with all the arguments set out in this book, I do think it has challenged my thinking on the topic. I recommend this to all individuals (non-scientists especially), especially that the writing style is very to read and follow.

[Alberto Tebaldi · Rating 4 out of 5]

sometimes hard to follow, but overall interesting topic

[Jennifer Myers]

I'll admit to skimming portions of this book when the science got to be too much for me, but the concept is timely. What if we had easy/free access to be able to decide many, many things about our unborn children? Even more than we do today... sex, athletic ability, diseases, etc. and not only would we find out more, but we'd be able to choose before the baby is even born- and maybe even have this baby grow in an artificial womb. Lots of things to ponder here, including many ethical and medical decisions. As a human who likes to see advances in technology but is also nervous about what may be invented that wipes us away, this is a great topic.