Reproduction In Humans - Article

 

Speculating The Future Of Human Reproduction

If your mom could bear your child, would you do it? And if so, on what grounds? The provocative, speculative artwork ‘Grandmom Mom’ raises these and more ethical questions on artificial reproduction in the nearby future. On the 8th of July, Waag hosted a livestream with bio-artist, speculative designer and former dentist Kuang-Yi Ku, where he presented his project. One of his driving ideas behind the project was to not postpone ethical reflection on such important matters until the technology arrives - you’re invited to think ahead with us.

The programme consisted of a presentation by the artist Kuang-Yi Ku, followed by a VR film screening on the Grandmom Mom narrative. Also part of the programme was Next Nature Networks’ researcher Hendrik-Jan Grievink, who gave a short presentation of their work ‘Reprodutopia’. The livestream finished with a panel talk, where some interesting questions and answers on artificial reproduction were raised.

The speculative narrative: Grandmom MomDuring his education as a dentist in the medical department, Kuang-Yi Ku noticed that there wasn’t much room for raising ethical questions. That’s why he’s now combining research questions with art. Although he is currently working as a bio-artist and a speculative designer, his work often relates to medical technology: ‘I’m interested in how medicine can combat future human challenges.’ Ku is based in Eindhoven and has worked with Waag before as an artist in residence in 2018.

Grandmom Mom’ is a futuristic scenario, set in 2050. Kuang-Yi Ku placed the Medical Geriatric Pregnancy Center in this nearby future. The luxurious, expensive-looking institution houses a new medical care system, that combines long-term care with a hospital of obstetrics and gynecology, a postpartum care centre and an infant care centre. It’s a medical service system in which grandmothers can help their daughters, by bearing their children. 

Outsourcing our sex organsBut first up in the programme was researcher Hendrik-Jan Grievink from Next Nature Network (NNN). Grievink: ‘I got interested in the question of new emerging reproductive qualities that change the story we as humans tell ourselves. We’re storytelling animals, and therefore, we surround ourselves with all kinds of mythologies. New technologies challenge us to rethink those stories.’ 

‘From a biological point of perspective, reproduction means sex. Humans like to bring intimacy and values into that, but technically it’s the species' attempt to survive by creating a new generation.’ Grievink notices how intimacy between humans has been severed by technologies such as IVF, embryo selection and artificial wombs. ‘From a design perspective: to what extent will intimacy be outsourced by technology? Will we outsource our sex organs?’

Design your family in ReprodutopiaIf there were no restraints, how would you design your family? This is Reprodutopia. Grievink: ‘We provide stories like Reproductopia to see what people would imagine for themselves. What does it mean to be human? Might artificial reproduction be an opportunity to improve gender equality, because the childbearing doesn’t have to be done by people of a certain gender and age?’ Threats, weaknesses and strengths of such plans can also be addressed.

Reprodutopia was also turned into a clinical, mobile environment that was showcased during Dutch Design Week at the Embassy of Health. There, one could for example try on a wearable artificial womb, with which they could engage and record their feelings, fears, hopes and dreams. Reproductopia also created visuals of pregnant men, and a visual map of the imagined Reprodutopia place, consisting of four countries, allowing the visitor to decide where they feel most (or least) comfortable.

The idea behind Grandmom MomLet’s return to ‘Grandmom Mom’ and the reason why the artist would suggest the scenario of grandmothers bearing their daughters' children. One of the reasons is the ‘jaw-dropping global crash in children being born’, as the header of an article states. On the one hand, Kuang-Yi Ku sees the reason for this in women who’d like to be able to work on their careers. ‘But it’s also a dilemma: by working, aren’t women just serving the capitalist system? Is it then utopian or dystopian? I’m inviting the public to rethink the issue of childbearing at a certain age.’

He continues: ‘The institutionalisation presented in Grandmom Mom also reinforces a constructed fragility, where the institution tries to control all female bodies to maintain the needs of the capitalist world.’

Kuang-Yi Ku also points out the cultural differences within parent-child relationships. ‘In Asia, there’s a very strong bond between the parent and child.’ Often, this leads to high pressure for children from their parents, who want them to reproduce the next generation. Ku points out that Asian parents might be more willing to bear their children’s offspring then maybe European or western parents would be. 

On creating the Virtual Reality of Grandmom MomIn order to create a persuasive and realistic Medical Geriatric Pregnancy Center, artist Kuang-Yi Ku started talking to medical consultants. ‘If elderly women get pregnant, there are certain risks. But if they are well taken care of, it could be possible. I tried to imagine if technologies can get upscaled. What kind of services are provided to elderly women and what would they look like in the institution of the International Geriatric Pregnancy Center?’

To fully involve people with the speculative narrative of Grandmom Mom, he collaborated with film director Lungyin Lim. ‘The idea of Virtual Reality (VR) took a long time to finalise,’ the director explains. ‘Kuang-Yi had a futuristic scenario in mind, and we spent a lot of time trying to convey the idea. As a filmmaker, I wanted to find the best tool to support the narrative. The moment you put in certain angles or lights, you already start framing. We wanted to keep some things open, and virtual reality allowed that.’

‘Virtual reality provides the opportunity to put you in a different space, and to let you be the decision maker on what you’d like to see.’ With the arrows in the VR, you can freely move around in the Medical Geriatric center. The aesthetics of the lighting and costumes look very pleasing and well-thought through. ‘The difference between VR and traditional formats is that we take a step back to let you see and feel. That’s one of the key elements: how would you make a choice, and how would it affect you?’ 

VR film screening

The beautifully designed human bodyAfter the screening, a panel discussion followed, with Kuang-Yi Ku, Hendrik-Jan Grievink, dr. Chen Yu Ping (gynecologist and midwife), dr. Yu-Chieh Yang (School of Medicine, Taipei Medical University) and filmmaker Lungyin Lim. Lucas Evers of Waag moderated the discussion.

When asked how the speculative scenario of Grandmom Mom could be realised, dr. Yang starts off with expressing her hesitance towards the idea: ‘an artificial womb might solve some problems, but if we take evolution into account, the human body has its own design that is far more difficult and beautiful than the artificial version. The interaction between the fetus and its mother is irreplaceable.’ 

‘As a mom of two children, I can say that this is something you can’t replace artificially. But of course, we can see the motivations of gay couples or women who can’t get pregnant. When it gets commercialised and industrialised, though, I don’t see the added value behind it.’ 

Dr. Ping adds: ‘we’re actually encouraging women to use their own human power during childbirth, and to not use technology too much. But Kuang-Yi explained to us that this project evokes questions of what is natural, and what is birth.’

The mechanical womb as male fantasyLucas Evers then asked Hendrik-Jan Grievink the following: ‘historically, most of medical science has always been male-dominated and therefore, it can be male biased. Isn’t the mechanical womb as presented in Reprodutopia just a male fantasy?’

Grievink admits that he was also asking himself this question. ‘It all started with a discussion, where we were talking about having children, when my (female) partner said: “if you want a child, why don’t you get one yourself?” This sparked my imagination. Technology reflects our human values. It allows us to have a conversation with ourselves, even before the actual technology has arrived. Artificial reproduction isn’t something that I would like to see, but it does provide for a framework, and it can act as a conversation starter.’

Kuang-Yi Ku: ‘these ethical questions aren’t usually raised in medical departments. Medicine seems objective, but this of course is not the case. Doctors might have their own opinions. They are mostly against artificial reproduction, but still I convinced some of them to collaborate on this project. I made sure to include female doctors to take their perspective into account.’ 

Then, someone in the livestream chat asks: ‘would you put your own mother at risk of illness to grow your baby?’ Kuang-Yi states: ‘this is a crucial question for the project. As a gay man, reproduction is not a possibility for myself and my partner. I would need a female surrogate. But should it be my own mother? And should we want that in a more general sense? It depends. In Asian culture, parents sacrifice themselves for their kids. Grandmom Mom questions these traditional parent-child relations.’

Speculation and dystopian scenariosShould these new reproductive technologies be available to everyone? Hendrik-Jan Grievink reflects on the term ‘techno-privilege’: it is important to take a critical look at the way technologies can privilege only certain groups of people, or create a divide between humans, non-humans and technology. But he also adds: ‘once you bring a group of people together, the discussion is always the same. The arguments in future speculation on technologies are mostly about the mechanics. It’s easier to look at the dystopian effects of stories, then to actually create a utopian scenario that people would actually want to live in.’

Kuang-Yi Ku: ‘My previous project, The Tiger Penis Project, is one I would really like to see realised in a utopian sense, because it saves tigers and traditional medicine. ‘Grandmom Mom’ is of course a bit more dystopian. In Taiwan, there are many traditional groups that want to erase all sex education. That’s why, also, sometimes I just want to scare people by creating a speculative narrative. But I agree with Hendrik-Jan: positive speculations for the future are the most difficult to create.’

Discrimination against pregnant womenA last question from the public expresses the worry of artificial reproduction as an amplification of gender inequality. ‘Will pregnant women be discriminated in the future, if they themselves want to become pregnant and will therefore not work [in the sense of paid work] for a while?’

Onto which dr. Yang answers: ‘Discrimination against pregnant women is already a reality. In the Netherlands it might be different. But bearing and raising a child is a very big job. It needs social support and that’s far from enough right now, in Taiwan. In the future society, you’d like to see more social support.’

Living With Relatives Offsets The Harm Caused By Pathogens In Natural Populations

Reviewer #1 (Recommendations for the authors):

I was surprised to read that among the key words used at different stages of the refinement process for the literature search, term like: clone, clonal, social,.… did not show up.

We initially tried combinations of search terms to identify those that increased the number of relevant papers without inflating the number of search hits. Relevant papers that used clone and clonal also used genetic diversity and monoculture and were therefore captured by our searches, but returned many hits from agricultural studies which we wanted to exclude. The term social was too broad, dramatically increasing our search hits. Relevant papers that used social also used the terms group, colony or relatedness and so we are confident that are search criteria captured relevant papers associated with these extra key words.

We have now clarified this point in the methods, section ‘Literature searches’ which reads:

“Initial exploration of search terms included other words (‘clone’,’clonal’,’social’). However, these terms inflated the number of search hits and papers with relevant data were retrieved using other terms included in our search criteria (‘group’, ‘colony’ or ‘relatedness’)” (Lines 276-279).

A focus of the study is on effects on mortality. However, many pathogens are hardly lethal, but reduce other fitness relevant traits strongly, such as competitive ability, work performance, sexual attractiveness and fecundity.

We agree that pathogens can have varied effects on different fitness related traits beyond mortality that are likely important for individuals. However, the relationship between within-group relatedness and measures such as fecundity can vary for many reasons other than pathogens making interpretation complicated. For example, local mate competition theory predicts that investment in sexual traits varies with local relatedness among individuals. Furthermore, traits such as sexual attractiveness and competitive ability are not easily interpreted in some species. In social insects, the relationship between relatedness and average attractiveness or competitive ability of workers does not have clear meaning to the hypotheses we tested. We therefore decided to stick with measures (mortality and pathogen abundance) that clearly related to the hypotheses we tested and that were comparable across all species.

We have now clarified in the methods why we excluded studies using other proxies of fitness. It reads:

“We did not include studies examining the relationship between within-group relatedness and other fitness related measures, such as fecundity or competitive ability, because such measures are influenced by factors other than pathogens” (Lines293-295).

Hand-picked examples of individual studies read nice and are entertaining, but they do not support the overall conclusion, but rather bias the observer. I suggest to leave them out, unless of specific relevance. E.G. The example of the frog and house mouse at the beginning of the result section, is not needed. Likewise the Tribolium and the worm examples (line 149).

We are grateful for the suggestion. We did not intend to bias the observer, but to give the reader greater insight into the primary studies. Meta-analyses can help cut through the species-specific idiosyncrasies allowing more general interpretation, but one downside is that the reader is left wondering what kind of studies were included. For this reason, we believe some examples can increase interpretability. Nevertheless, we have reduced these (example at the start of the results removed) in accordance with the referee’s suggestion.

Reviewer #2 (Recommendations for the authors):

– 38. I have not checked but remember that Baer and Schmid-Hempel (you cite these papers) had a more direct experimental manipulation approach than Liersch and Schmid-Hempel because they inseminated bumblebee queens with either 1 or 4 ejaculates. Worth citing here too?

We have now added this citation.

– 44. Why is extinction risk relevant? Natural selection only sees individual inclusive fitness. Rephrase to avoid ambiguity?

We have now rephrased this, which reads:

“What remains unclear, however, is whether this translates into higher rates of mortality, or whether the benefits of living with relatives are large enough to offset the costs of increased disease risk” (Lines 49-51).

– 57-60. Unclear sentence – rephrase.

We have revised this sentence, which reads:

“For instance, a negative relationship between relatedness and the abundance of pathogens can occur either because groups of relatives are less susceptible to pathogens, or conversely because groups of relatives frequently die from pathogens and so rarely observed” (Lines 62-65).

– 67. It was Sylvia Cremer who developed the field of 'social immunity' in the first decade of this century. I think that pioneering work should be cited here. You have one of her papers (Ugelvig et al), but possibly the review by Cremer and Sixt is more general.

Thank you for the suggestion. We now cite Ugelvig et al. As well as Cremer and Sixt.

– 79. Replace the second 'to' by 'as in' to make sentence clearer?

Addressed.

– 106. It seems rather excessive to use three decimals here.

Agreed! The manuscript is written in R markdown so results can be directly inserted into text to increase reproducibility, but sometimes the formatting slips through the net. We have now changed the results to 2 decimals throughout.

– 191-193. As in 44, the phrasing seems to have a slight and I'm sure unintentional group-selection slant. Can some rewording repair that?

We have now rephrased this sentence which reads:

“One explanation is that individuals respond to greater pathogen pressure by forming more genetically diverse groups” (Lines 210-211).

– 205-207: In Acromyrmex individuals are non-totipotent caste members and they do not have a 'choice' between living with relatives of non-relatives. Further, relatedness in Acromyrmex colonies is very low for ant standards, so even though you have them in the high relatedness (>0.25) category, they would be in the low-relatedness category when you would focus on social Hymenoptera only. The Hughes papers that you cite have precise relatedness estimates I believe. Somehow the phrasing of your text does not seem to capture these peculiarities.

This example was to illustrate that spatial segregation and task partitioning within groups can reduce the spread of pathogen transmission among group members. While Acromyrmex have lower (derived) relatedness than some other social insects, they still have relatively high relatedness compared to the other species in our dataset (E.G. Acromyrmex octospinosus: r = ca. 0.33, Boomsma et al. 1999. Acromyrmex echinatior r = 0.380±0.042 Sumner et al. 2004). We have tried to rephrase this section to clarify the point of this example.

It reads:

“For example, in leaf cutter ants, Acromyrmex spp, workers outside the colony, where pathogens are more prevalent, do not enter the inner colony (Camargo et al., 2007). Contamination of food by pathogens is also limited by workers outside the colony performing dedicated tasks, such as foraging versus waste management (Waddington and Hughes, 2010)” (Lines 200-204).

– The numerical order of the supplementary tables seems rather haphazard. Should they not be numbered in the order they are presented in the text?

Thank you for pointing this out. The supplementary tables are now numbered in the order they appear in the text.

https://doi.Org/10.7554/eLife.66649.Sa2

Eavesdropping On Hormones To Help Understand Reproduction

Me at the San Diego Zoo Safari Park in 2007 or so.

Every vertebrate on the planet has evolved a complex system that uses small molecules called hormones to communicate directives to isolated tissues that impact everything in the body from eating to producing babies. This hormonal communication between tissues is critical during reproductive processes. From the production of eggs and sperm, to placenta development, to birth, tissues are in constant hormonal communication.

At the National Institute of Standards and Technology (NIST) in the Hollings Marine Laboratory in Charleston, South Carolina, I measure hormones in the hopes of deciphering the communications between these tissues. Basically, I’m a biological eavesdropper, and like any good eavesdropper, I must know all the details to truly understand a story. However, for years, people who study hormones, known as endocrinologists, have been measuring single hormones at a time, and these individual measurements only told a small part of the biological story.

Single hormones found in blood don’t tell the eavesdropper where they came from and where they went. You see, these single hormones studied are almost always modified into hormone metabolites by different tissues. A combination of these metabolites is a hormone profile or unique hormonal “dialect” that tissues use to communicate specific directives. Measuring these metabolites will allow endocrinologists to listen to the body’s hormonal story for further understanding of biological systems.

Within biological systems, my main interest is the story of reproduction. I use a technique known as liquid chromatography mass spectrometry (LC-MS) to measure hormones and their metabolites. This technology allows me to accurately measure at least 20 different hormones at one time, providing a hormone profile for each tissue so I can better understand the full reproductive conversation. For example, measuring the hormone progesterone can tell you a horse is pregnant, but measuring progesterone plus six other hormones and hormone metabolites can tell you exactly how far along the pregnancy is down to a few weeks. We can apply this concept to animal agriculture production, wildlife conservation and even human fetal and maternal health during pregnancy.

As a National Research Council (NRC) postdoctoral fellow here at NIST, I am working on a project to help solve the mystery of why the fertility rate of Atlantic salmon has dropped 30% in the past 20 years. To understand what’s going on reproductively in these economically important fish, we measure hormones in Atlantic salmon mucus.

But wait, you might say, aren’t hormones in blood? Yes, yes, they are! Well, then, why muck around with mucus?

There are many ways to measure hormones that don’t require a needle. Besides fish mucus, hormones can be found in feces, saliva, hair, milk, feathers and even baleen, providing many alternative methods to study hormones in animals. It’s markedly easier to collect mucus from a fish or urine from a cheetah than blood. These alternative sample collection methods are important for measuring hormones not only in wild animals but humans as well. What pregnant woman would choose to be poked 500 times with a needle rather than pee in a cup?

In conjunction with the USDA’s National Cold Water Marine Aquaculture Center, I collected mucus samples from reproductively active fish with the hope of decoding the hormonal conversation of highly fertile fish. If we can identify this “highly fertile” hormone profile, then producers will be able to select those fish for breeding, thereby improving the Atlantic salmon fertility rate.

My investigation into noninvasive measures of hormones using fish mucus reminded me of the days I spent collecting fecal samples as a zookeeper at the San Diego Zoo Safari Park and analyzing them at the San Diego Zoo Wildlife Alliance. It was there that I was first introduced to the idea of noninvasively monitoring wildlife reproduction through hormones in feces. Although, let me tell you, getting hormones out of feces is about as stinky as it gets! Stinky or not, I loved the work and thought, “Hey, maybe other institutions would be just as interested in noninvasive hormone measurements as I am!”

It turns out there were two organizations that jumped at the chance: the National Institute of Environmental Health Sciences (NIEHS), which is part of the National Institutes of Health, and the Smithsonian Conservation Biology Institute (SCBI). Both institutions were interested in NIST’s unique ability to measure steroid hormones with liquid chromatography high resolution mass spectrometry (LC-HRMS) and tandem mass spectrometry (LC-MS/MS) to enhance their respective reproductive programs. These technologies will be used to first identify (LC-HRMS) and then measure (LC-MS/MS) hormone metabolites in the urine of pregnant animals: humans and cheetahs, respectively.

Endocrinologists love to say “Hormones didn’t evolve to fit the animal. Animals evolved to fit the hormone.” Or, simply put, the progesterone from the Atlantic salmon looks exactly the same as human or cheetah progesterone. However, each of these animals use and metabolize progesterone differently during different reproductive events, resulting in two institutions asking very different questions (on different species) that we can answer with one measurement method.

The question from NIEHS concentrates on early pregnancy health in women and started way back in the 1980s. Between 1982-1986, women collected urine daily from the first day of their last period before they got pregnant until they were eight weeks pregnant. We’re talking over 10,000 urine samples! This remarkable data set was collected by a group led by Donna Baird who wanted to study early pregnancy. When I reached out, both Donna and her colleague Anne Marie Jukic immediately thought of this sample set, and together, we are working to identify the hormone metabolites that can detect both the timing and health of pregnancy.

To do this, there are two pregnancy outcomes in this study: One group had pregnancies that went to full term, and the other group miscarried after eight weeks. Within these two groups there were three distinct time points that center around placental development. In measuring urinary hormone metabolites at the early stages of placental development, we hope to identify a hormone profile that indicates the health of the placenta and potentially fetal health. This information can help doctors better care for their patients and prevent pregnancy loss.

SCBI was also interested in this project to improve the care of its patients! Animals don’t speak “human,” so our only way of communicating with them is with physiological biomarkers. If SCBI could measure hormone metabolites in the urine of endangered animals, we might be able to describe their reproductive processes in more detail and determine reasons for infertility and pregnancy loss. Understanding these issues is also key if we’re going to help save animals from extinction.

SCBI had an impressive urine bank from pregnant cheetahs and was excited to use these samples to study cheetah reproduction. You see, cheetahs are tricky. They breed really well in the wild but poorly in captivity. Unfortunately, in the wild they’re being hunted and losing habitat to the point that cheetah numbers are extremely low. Adrienne Crosier at SCBI focuses on understanding fundamental carnivore biology to improve reproduction, and she is specifically interested in understanding causes of infertility in big cats, primarily cheetahs. Adrienne, along with Janine Brown and Budhan Pukazhenthi, expressed interest in using LC-MS technologies to identify the hormone metabolites that differ between pregnant and nonpregnant cheetahs.

Just as cheetahs use spots for camouflage, their bodies use progesterone to camouflage pregnancy. Once a cheetah breeds, she releases the same amount of progesterone no matter if she’s pregnant or not pregnant. This phenomenon is called pseudopregnancy and occurs in many carnivores. A single hormone can’t help us detect a pregnant cheetah, but a hormone profile will hopefully define placental metabolism of hormones in cheetahs and give researchers a reliable detection method to improve the management of these charismatic cats. On a personal note, I was extremely excited to work with wildlife again. It felt like my original training in wildlife endocrinology had come full circle.

Whether I’m measuring hormones in fish mucus to study ovulation or urinary hormone metabolites to measure healthy pregnancies, I am always grateful that I get to work on what I love! I get to be a biological eavesdropper on the reproduction of animals. And I do have to say … that’s pretty amazing!