I weighed 7 pounds, 7 ounces when I was born on Saturday, 9 March 1957, at 7:07 in the morning. I know this because all the 7s were memorable, but mainly because this is what doctors and nurses do: they document everything.

You know this. Everytime we visit a doctor, they write down our weight, our height, our blood pressure, every parameter they can squeeze out of us. I can go online right now and read the doctor’s notes on every medical visit I’ve made in the last 20-some years — every prescription, every measurement, all of my complaints, every recommendation, every vaccination…it’s all there. Doctors are obsessive record keepers. There is so much medical data stored away that I sometimes wonder how anyone can extract useful information from it.

But they have! One attempt that has had significant influence was to correlate birth weight data in infants with their adult history of cardiovascular disease. Surprise, your weight on the day you were born is associated with your blood pressure, 60 years later (in a broad statistical sense, of course — this is a population-level correlation.) This led David Barker to make the specific hypothesis that “poor nutrition, health and development among girls and young women is the origin of high death rates from cardiovascular disease in the next generation.” This idea has since been broadened to form the developmental origin of adult disease hypothesis, that all kinds of medical phenomena have their origns in fetal development, and in the environmental effects that have influenced that development.

Credit where credit is due, the original exploration of the hypothesis was thanks to careful records kept by one midwife, Margaret Burnside, who assisted in the birth of over 15,000 babies in Hertfordshire between 1911 and 1930, and also the records of over 2000 births at Jessop Hospital in Sheffield between 1907 and 1924. They then compared birth records with death certificates in the 1950s-1990s to extract the first hints of associations.*

There’s a huge industry of papers being turned out now that look at correlations between birth weight and adult medical conditions. We’re also seeing more complex connections between disease and growth rate in the first year.

Some of them are very well established associations with low birth weight, like hypertension, coronary artery disease, non-insulin dependent diabetes, stroke, dislipidaemia, elevated clotting factors, and impaired neurodevelopment. Other ‘problems’ have been associated with low birth weight in a small number of studies — there really are amazing numbers of papers where researchers mine the medical data for connections, some of them possibly spurious. So small babies may be more likely to develop issues with chronic lung disease, depression, schizophrenia, and general behavioral problems. They may have reduced uterine and ovarian size and precocious pubarche. They might be more prone to breast and testicular cancer.

Surprisingly, they may also marry later, if at all, be left-handed, and have denser fingerprint whorls. You can find it all in the scientific literature.

If you are thinking that you were a plump, fat baby, so you have nothing to worry about, think again. There are correlations between large birth weight and breast cancer (everything seems to cause breast cancer,) prostate cancer, childhood leukemia, and polycystic ovary disease.

This week in my eco devo course, we talked about this hypothesis, and I also handed out a bunch of papers, a different one for each student (there are so many papers in this field!), and today we’re going to have the students assess the literature. It should be fun! The goal is to get a feel for how strong or how valid the various correlations actually are. We’ve also discussed the Dutch famine data. The Nazis starved much of Holland, including the major cities of Rotterdam, Amsterdam, and Leiden, for 7 months in 1945, until the country was liberated by the Allies.

Wasn’t that nice of Nazis to do a massive experiment on a whole nation of 9 million people for us? They let women in each trimester of their pregnancy subsist on 580 calories/day, and then went away and let us analyze the effects. Maternal malnutrition in the third trimester turns out to be bad for babies, who knew? Anyway, the subtext for this week, as it should be for every week, is that Nazis are bad***.

The bigger message is, of course, that development matters and has lifelong consequences, and good, responsible governments provide adequate nutrition to pregnant women and children.

*All these records were handwritten on pieces of paper! The effort to transcribe everything and extract the information in a computational form must have been daunting.**

**My daughter is currently involved in a research project to use natural language processing to synthesize information stored in modern medical records at UW Madison Department of Medicine. That’s useful for a lot of reasons, including drilling down through years of impenetrable treatment notes.

***I hope that overtly political message doesn’t get me in trouble with the university administration.

In my eco devo course, we’ve been looking at increasingly subtle effects. We started out the semester examining obviously devastating agents in the environment — think thalidomide, stuff that outright kills embryos or causes gross distortions of developmental processes. Then we spent a few weeks looking at endocrine disruptors, agents that perturb developmental signaling and produce embryos with, for example, fertility problems or changes in sexual differentiation. There are a lot of ways chemistry can screw you up short of wrecking external morphology!

This past week we also looked at micro- and nanoplastics, which I personally find have the potential to be a colossal nightmare. The US is producing about 75 million tons of plastic waste each year, and that crap doesn’t go away. You can throw it in a landfill or dump it in the ocean, but it is just physically eroded down into smaller and smaller fragments, allowing it to infiltrate ever deeper into us and our world. Did you know that archaeologists are finding microplastics drifting down into soils 7 meters down, and that they’re finding them in thousand year old sites? We are filling the world with these novel stable polymers, and we have a poor idea of what they’re doing to us.

So we read a paper by Pederson et al. (2020) about the effect of nanoplastics on zebrafish embryos. Like every paper on this kind of topic, it has to tell us about the magnitude of the problem.

Plastic pollution is ubiquitous and an emerging concern in both freshwater and marine environments. Since mass production began in the 1940s, plastic manufacturing has increased rapidly, with 348 million tons produced globally in 2018. Large amounts end up in the oceans, which are now predicted to contain more than five trillion individual pieces of plastic materials (equaling 250,000 tons) in the first 20 m of the water column. Plastics have been identified virtually everywhere: from arctic sea ice to ocean sediments. In freshwater systems, plastics have been identified in large quantities in lakes, rivers, and basins, especially in areas near dense human populations. Their ubiquity has allowed for potential human exposure to plastics through the consumption of aquatic organisms and via drinking water, especially due to the inability of drinking water facilities to entirely remove anthropogenic particles sourced through freshwater environments. In 2019, the World Health Organization (WHO) called for a greater assessment of plastics in the environment after 90% of bottled water was found to contain small plastic particles (World Health Organization). In addition, anthropogenic particles, many of which are likely plastic fragments and fibers, have been detected in over 81% of tap water sources, allowing for an average of 5800 particles to be ingested annually per person.

This paper isn’t even talking about familiar microplastics — it’s all about nanoplastics, particles less than 1µm in diameter. Eventually, all plastics will be broken down to that degree, but we give these an additional boost by intentionally synthesizing these for use in toothpastes and cosmetics and cleansers, and we’ve added <1 parts per billion (ppb) to tens of thousands of ppb to freshwater and marine ecosystems. We don’t have a practical way to remove this stuff. Go ahead, take a swig of that water bottled in plastic, you’ll just absorb those exotic polymers, they’ll be circulating in your bloodstream and getting incorporated into your tissues. You’ll hardly notice.

Zebrafish embryos and larvae swimming in a solution of up to 10000 ppb nanoplastics didn’t seem to mind. There was no effect on mortality, no change in growth rate, no apparent deformities at all. Maybe we’ll all be OK after all.

Except…they do visibly accumulate the plastics in their tissues (they used plastics that fluoresce in the UV).

And then they looked at gene expression in various known pathways — metabolic genes, genes involved in nervous system function, the cardiovascular system — and whoa, they’re just shifted all over the place. It’s a sign of how robust development is that the organism was looking so normal to human eyes. We are all loaded with compensatory developmental mechanisms to make our construction more reliable, and it always impresses me how much damage and insult an embryo can take and still emerge fairly recognizable.

One disappointment in the paper is that the behavioral assays were fairly crude, but that’s not the investigators’ fault. They’re working with 5-day old larvae, which, while zebrafish are remarkable little sensory processing machines at that age, they’re still kind of stupid, with a limited behavioral repertoire. The authors looked at spontaneous motor activity, and the fish exhibited a dose-dependent increase in burst swimming. They’re twitchier. More hyperactive. Their brains are being randomly modified chemically, and we’re seeing changes that I’d expect to be more apparent with more sensitive assays.

The message I’m trying to get across to the students is that there is a wide range of phenomena that environmental factors are causing, and we don’t know most of them. It took us decades to get corporations to remove lead from our gasoline, despite the obvious ways it was perturbing our growth and behavior. Are plastics going to be the leaded gasoline of the 21st century?

There is a solution: make biodegradable plastics, ones that don’t reduce to dead stable particles, but instead are digestible by organisms and can be metabolized. Progress is being made in that direction!

An attractive solution to mitigate the environmental impact of microplastics is to develop plastics that do not generate persistent microplastics as part of their normal life cycle. Even plastics that are properly collected and recycled generate microplastics as part of the normal wear from everyday use or as a consequence of recycling or washing processes. Thus, to prevent the accumulation of microplastics, new plastic materials must be developed that are completely biodegradable so that any particles generated from these products will quickly degrade in the environment. Biodegradation is the process by which microbes break down polymers into simpler molecules that can be used as a source of carbon to produce biomass. This requires that the polymer contains chemical bonds, most notably in the polymer’s primary backbone structure, that are physically accessible to enzymes that naturally recognize these bonds as substrates, and that the underlying monomer molecules that are released through this enzymatic cleavage can be consumed by microorganisms. In natural environments, this process is typically performed by consortia of microbes, including bacteria and fungi, secreting hydrolytic enzymes, which sever the polymer to release a variety of monomers and oligomers that can then be utilized as a carbon nutrient source by the microbes. Catabolism of these polymer-derived oligomers and monomers leads to the generation of organismal biomass and CO2 via respiration.

Why would we want structural materials that inevitably break down? Well, maybe you don’t, but I think if we whisper “planned obsolescence” into the ears of corporate executives, maybe they’ll force us to accept them.

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Pedersen AF, Meyer DN, Petriv A-MV, Soto AL, Shields JN, Akemann C, Baker BB, Tsou W-L,
Zhang Y, Baker TR (2020) Nanoplastics impact the zebrafish (Danio rerio) transcriptome: Associated developmental and neurobehavioral consequences. Environmental Pollution https://doi.org/10.1016/j.envpol.2020.115090.