Why does the baby cry? Fact sheet.

Gloria at 2 months, crying.

Two weeks after delivery, when the husband went back to work and my hemoglobin level had recovered enough to let me think about anything besides breathing, I seemed to be spending a lot of time on The One Question: Why does the baby cry? We had been drowned in baby books that all had something helpful to say. Or so I believe, not having read them. But what really is the evolutional origin of all that crying to begin with? That’s what I was wondering. Is there a reason to begin with?

You don’t need a degree to know that baby cries if she’s unhappy. After a few weeks I had developed a trouble-shooting procedure roughly like this: Does she have a visible reason to be unhappy? Does she stop crying if I pick her up? New diaper? Clothes comfortable? Too warm? Too cold? Is she bored? Is it possible to distract her? Hungry? When I had reached the end of my list I’d start singing. The singing almost always helped. After that, there’s the stroller and white noise and earplugs.

Yes, the baby cries when she’s unhappy, no doubt about that. But both Lara and Gloria would sometimes cry for no apparent reason, or at least no reason that Stefan and I were able to figure out. The crying is distressing for the parents and costs the baby energy. So why, if it’s such an inefficient communication channel, does the baby cry so much? If the baby is trying to tell us something, why haven't hundred thousands of years of evolution been sufficient to teach caregivers what it is that she wants? I came up with the following hypotheses:

A) She doesn’t cry for any reason, it’s just what babies do. I wasn’t very convinced of this because it doesn’t actually explain anything.

B) She cries so I don’t misplace or forget about her. I wasn’t very convinced of this either because after two months or so, my brain had classified the crying as normal background noise. Also, babies seem to cry so much it overshoots the target: It doesn’t only remind the caregivers, it frustrates them.

C) It’s a stress-test. If the family can’t cope well, it’s of advantage for future reproductive success of the child if the family breaks up sooner rather than later.

D) It’s an adaption delay. The baby is evolutionary trained to expect something else than what it gets in modern western societies. If I’d just treat the baby like my ancestors did, she wouldn’t cry so much.

So I went and looked what the scientific literature has to say. I found a good review by Joseph Soltis from the year 2004 which you can download here. The below is my summary of these 48 pages.

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First, let us clarify what we’re talking about. The crying of human infants changes after about 3 months because the baby learns to make more complex sounds and also becomes more interactive. In the following we’ll only consider the first three months that are most likely to be nature rather than nurture.

Here are some facts about the first three months of baby’s crying that seem to be established pretty well. All references can be found in Soltis’ paper.

• Crying increases until about 6 weeks after birth, followed by a gradual decrease in crying until 3 or 4 months, after which it remains relatively stable. Crying is more frequent in the later afternoon and early evening hours. These crying patterns have been found in studies of very different cultures, from the Netherlands, from South African hunter-gatherers, from the UK, Manilia, Denmark, and North America.
• Chimpanzees too have a peak in crying frequency at approximately 6 weeks of life, and a substantial decline in crying frequency by 12 weeks.
• The cries of healthy, non-stressed infants last on the average 0.5-1.5 seconds with a fundamental pitch in the range of 200-600 Hz. The melody is either falling or rising/falling (as opposed to rising, falling/rising or flat).
• Serious illness, both genetic and acquired, is often accompanied by abnormal crying. The most common cry characteristic indicating serious pathology is an unusually high pitched cry, in one case study above 2000 Hz, and in many other studies exceeding 1500 Hz. (That’s higher than most sopranos can sing.) Examples are: bacterial meningitis 750-1000 Hz, Krabbe’s disease up to 1120 Hz, hypoglycemia up to 1600 Hz. Other abnormal cry patters that have been found in illness is biphonation (the simultaneous production of two fundamental frequencies), too low pitch, and deviations from the normal cry melodies.
• Various studies have been conducted to find out how well adults are able to tell the reason for a baby’s cry by playing them previously recorded cries. These studies show mothers are a little bit better than random chance when given a predefined selection of choices (eg pain, anger, other, in one study), but by and large mothers as well as other adults are pretty bad at figuring out the reason for a baby’s cry. Without being given categories, participants tend to attribute all cries to hunger.
• It has been reported in several papers that parents described a baby’s crying as the most proximate cause triggering abuse and infanticide. It has also been shown that especially the high pitched baby cries produce a response of the autonomic nervous system, measureable for example by the heart rate or skin conductance (the response is higher than for smiling babies). It has also been shown that abusers exhibit higher autonomic responses to high-pitched cries than non-abusers.
• Excessive infant crying is the most common clinical complaint of mothers with infants under three months of age.
• Excessive infant crying that begins and ends without warning is called “colic.” It is often attributed to organic disorders, but if the baby has no other symptoms it is estimated that only 5-10% of “colic” go back to an organic disorder, the most common one being lactose intolerance. If the baby has other symptoms (flexed legs, spasm, bloating, diarrhea), the ratio of organic disorder goes up to 45%. The rest cries for unknown reasons. Colic usually improves by 4 months, or so they tell you. (Lara’s didn’t improve until she was 6 months. Gloria never had any.)
• Colic is correlated with postpartum depression which is in turn robustly associated with reduced maternal care.
• Records and media reports kept by the National Center on Shaken Baby Syndrome implicate crying as the most common trigger.
• In a survey among US mothers, more infant crying was associated with lower levels of perceived infant health, more worry about baby’s health, and less positive emotion towards the infant.
• Some crying bouts are demonstrably unsoothable to typical caregiving responses in the first three months. Well, somebody has to do these studies.
• In studies of nurses judging infant pain, the audible cry was mostly redundant to facial activity in the judgment of pain.

Now let us look at the hypotheses researchers have put forward and how well they are supported by the facts. Again, let me mention that everybody agrees the baby cries when in distress, the question is if that’s the entire reason.

1. Honest signal of need. The baby cries if and only if she needs or wants something, and she cries to alert the caregivers of that need. This hypothesis is not well supported by the facts. Baby’s cries are demonstrably inefficient of bringing the baby the care it allegedly needs because caregivers don’t know what she wants and in many cases there doesn’t seem to be anything they can do about it. This is the scientific equivalent of my hypothesis D which I found not so convincing.
2. Signal of vigor. This hypothesis says that the baby cries to show she’s healthy. The more the baby cries (in the “healthy” pitch and melody range), the stronger she is and the more the mother should care because it’s a good investment of her attention to raise offspring that’s likely to reproduce successfully. Unfortunately, there’s no evidence linking a high amount of crying to good health of the child. In contrast, as mentioned above, parents perceive children as more sickly if they cry more, which is exactly the opposite of what the baby allegedly “wants” to signal. Also, lots of crying is apparently maladaptive according to the evidence listed above, because it can cause violence against the child. It’s also unclear why, if the baby isn’t seriously sick and too weak to cry, a not-so-vigorous child should alert the caregivers to his lack of vigor and trigger neglect. It doesn’t seem to make much sense. This is the scientific equivalent of my hypothesis B which I didn’t find very convincing either.
3. Graded signal of distress. The baby cries if she’s in distress, and the more distress the more she cries. This hypothesis is, at least for what pain is concerned, supported by evidence. Pretty much everybody seems to agree on that. As mentioned above however, while distress leads to crying, this leaves open the question why the baby is in distress to begin with and why it cries if caregivers can’t do anything about it. Thus, while this hypothesis is the least controversial one, it’s also the one with the smallest explanatory value.
4. Manipulation: The baby cries so mommy feeds her as often as possible. Breastfeeding stimulates the production of the hormone prolactin; prolactin inhibits estrogen production, which often (though not always) keeps the estrogen level below the threshold necessary for the menstrual cycle to set it. This is called lactational amenorrhea. In other words, the more the baby gets mommy to feed her, the smaller the probability that a younger sibling will compete for resources, thus improving the baby’s own well-being. The problem with this hypothesis is that it would predict the crying to increase when the mother’s body has recovered, some months after birth, and is in shape to carry another child. Instead however, at this time the babies cry less rather than more. (It also seems to say that having siblings is a disadvantage to one’s own reproductive success, which is quite a bold statement in my opinion.)
5. Thermoregulatory assistance. An infant’s thermoregulation is not very well developed, which is why you have to be so careful to wrap them warm when it’s cold and to keep them in the shade when it’s hot. According to this hypothesis the baby cries to make herself warm and also to alert the mother that it needs assistance with thermoregulation. It’s an interesting hypothesis that I hadn’t heard of before and it doesn’t seem to have been much studied. I would expect however that in this case the amount of crying depends on the external temperature, and I haven’t come across any evidence for that.
6. Inadequacy of central arousal. The infant’s brain needs a certain level of arousal for proper development. Baby starts crying if not enough is going on, to upset herself and her parents. If there’s any factual evidence speaking for this I don’t know of it. It seems to be a very young hypothesis. I’m not sure how this is compatible with my finding that the Lara after excessive crying would usually fall asleep, frequently in the middle of a cry, and that excitement (people, travel, noise) were a cause for crying too.
7. Underdeveloped circadian rhythm. The infant’s sleep-wake cycle is very different from an adult’s. Young babies basically don’t differentiate night from day. It’s only at around two to three months that they start sleeping through the night and develop a daily rhythm. According to this hypothesis it’s the underdeveloped circadian rhythm that causes the baby distress, probably because certain brain areas are not well synched with other daily variations. This makes a certain sense because it offers a possible explanation for the daily return of crying bouts in the late afternoon, and also for why they fade when the babies sleep through the night. This too is a very young hypothesis that is waiting for good evidence.
8. Behavioral state. The baby’s mind knows three states: Sleep, awake, and crying. It’s a very minimalistic hypothesis, but I’m not sure it explains anything. This is the scientific equivalent of my hypothesis A, the baby just cries.

Apparently nobody ever considered my hypothesis D, that baby cries to move herself into an optimally stable social environment which would have developmental payoffs. It’s probably very difficult a case to make. The theoretical physicist in me is admittedly most attracted to one of the neat and tidy explanations in which the crying is a side-effect of a physical development.

So if your baby is crying and you don’t know why, don’t worry. Even scientists who have spent their whole career on this question don’t actually know why the baby cries.

Book Review: "The Quest for the Cure" by B.R. Stockwell

The Quest for the Cure: The Science and Stories Behind the Next Generation of Medicines
By Brent R. Stockwell
Columbia University Press (June 1, 2011)

As a particle physicist, I am always amazed when I read about recent advances in biochemistry. For what I am concerned, the human body is made of ups and downs and electrons, kept together by photons and gluons - and that's pretty much it. But in biochemistry, they have all these educated sounding words. They have enzymes and aminoacids, they have proteases, peptides and kineases. They have a lot of proteins, and molecules with fancy names used to drug them. And these things do stuff. Like break up and fold and bind together. All these fancy sounding things and their interactions is what makes your body work; they decide over your health and your demise.

With all that foreign terminology however, I've found it difficult to impossible to read any paper on the topic. In most cases, I don't even understand the title. If I make an effort, I have to look up every second word. I do just fine with the popular science accounts, but these always leave me wondering just how do they know this molecule does this and how do they know this protein breaks there, fits there, and that causes cancer and that blocks some cell-function? What are the techniques they use and how do they work?

When I came across Stockwell's book "The Quest for the Cure" I thought it would help me solve some of these mysteries. Stockwell himself is a professor for biology and chemistry at Columbia university. He's a guy with many well-cited papers. He knows words like oligonucleotides and is happy to tell you how to pronounce them: oh-lig-oh-NOOK-lee-oh-tide. Phosphodiesterase: FOS-foh-dai-ESS-ter-ays. Nicotinonitrile: NIH-koh-tin-oh-NIH-trayl. Erythropoitin: eh-REETH-roh-POIY-oh-ten. As a non-native speaker I want to complain that this pronunciation help isn't of much use for a non-phonetic language; I can think of at least three ways to pronounce the syllable "lig." But then that's not what I bought the book for anyway.

The starting point of "The Quest for the Cure" is a graph showing the drop in drug approvals since 1995. Stockwell sets out to first explain what is the origin of this trend and then what can be done about it. In a nutshell, the issue is that many diseases are caused by proteins which are today considered "undruggable" which means they are folded in a way that small molecules, that are suitable for creating drugs, can't bind to the proteins' surfaces. Unfortunately, it's only a small number of proteins that can be targeted by presently known drugs:

"Here is the surprising fact: All of the 20,000 or so drug products that ever have been approved by the U.S. Food and Drug Administration interact with just 2% of the proteins found in human cells."

And fewer than 15% are considered druggable at all.

Stockwell covers a lot of ground in his book, from the early days of genetics and chemistry to today's frontier of research. The first part of the book, in which he lays out the problem of the undruggable proteins, is very accessible and well-written. Evidently, a lot of thought went into it. It comes with stories of researchers and patients who were treated with new drugs, and how our understanding of diseases has improved. In the first chapters, every word is meticulously explained or technical terms are avoided to the level that "taken orally" has been replaced by "taken by mouth."

Unfortunately, the style deteriorates somewhat thereafter. To give you an impression, it starts more reading like this

"Although sorafenib was discovered and developed as an inhibitor of RAF, because of the similarity of many kinases, it also inhibits several other kinases, including the patelet-derived growth factor, the vascular endothelia growth factor (VEGF) receptors 2 and 3, and the c-KIT receptor."

Now the book contains a glossary, but it's incomplete (eg it neither contains VEGF nor c-KIT). With the large number of technical vocabulary, at some point it doesn't matter anymore if a word was introduced, because if it's not something you deal with every day it's difficult to keep in mind the names of all sorts of drugs and molecules. It gets worse if you put down the book for a day or two. This doesn't contribute to the readability of the book and is somewhat annoying if you realize that much of the terminology is never used again and one doesn't really know why it was necessary to use to begin with.

The second part of the book deals with the possibilities to overcome the problem of the undruggable molecules. In that part of the book, the stories of researchers curing patients are replaced with stories of the pharmaceutical industry, the start-up of companies and the ups and downs of their stock price.

Stockwell's explanations left me wanting in exactly the points that I would have been interested in. He writes for example a few pages about nuclear magnetic resonance and that it's routinely used to obtain high resolution 3-d pictures of small proteins. One does not however learn how this is actually done, other than that it requires "complicated magnetic manipulations" and "extremely sophisticated NMR methods." He spends a paragraph and an image on light-directed synthesis of peptides that is vague at best, and one learns that peptides can be "stapled" together, which improves their stability, yet one has no clue how this is done.

Now the book is extremely well referenced, and I could probably go and read the respective papers in Science. But then I would have hoped that Stockwell's book saves me exactly this effort.

On the upside, Stockwell does an amazingly good job communicating the relevance of basic research and the scientific method, and in my opinion this makes up for the above shortcomings. He tells stories of unexpected breakthroughs that came about by little more than coincidence, he writes about the relevance of negative results and control experiments, and how scientific research works:

"There is a popular notion about new ideas in science springing forth from a great mind fully formed in a dazzling eureka moment. In my experience this is not accurate. There are certainly sudden insights and ideas that apear to you from time to time. Many times, of course, a little further thought makes you realize it is really an absolutely terrible idea... But even when you have an exciting new idea, it begins as a raw, unprocessed idea. Some digging around in the literature will allow you to see what has been done before, and whether this idea is novel and likely to work. If the idea survives this stage, it is still full of problems and flaws, in both the content and the style of presenting it. However, the real processing comes from discussing the idea, informally at first... Then, as it is presented in seminars, each audience gives a series of comments, suggestions, and questions that help mold the idea into a better, sharper, and more robust proposal. Finally, there is the ultimate process of submission for publication, review and revision, and finally acceptance... The scientific process is a social process, where you refine your ideas through repeated discussions and presentations."

He also writes in a moderate dose about his own research and experience with the pharmaceutical industry.

The proposals that Stockwell has how to deal with the undruggable proteins have a solid basis in today's research. He isn't offering dreams or miracle cures, but points out hopeful recent developments, for example how it might be possible to use larger molecules. The problem with large molecules is that they tend to be less stable and don't enter cells readily, but he quotes research that shows possibilities to overcome this problem. He also explains the concept of a "privileged structure," structures that have been found with slight alterations to bind to several proteins. Using such privileged structures might allow one to sort through a vast parameter space of possible molecules with a higher success rate. He also talks about using naturally occurring structures and the difficulties with that. He ends his book by emphasizing the need for more research on this important problem of the undruggable proteins.

In summary: "The Quest for the Cure" is a well-written book, but it contains too many technical expressions, and in many places scientific explanations are vague or lacking. It comes with some figures which are very helpful, but there could have been more. You don't need to read the blurb to figure out that the author isn't a science writer but a researcher. I guess he's done his best, but I also think his editor should have dramatically sorted out the vocabulary or at least have insisted on a more complete glossary. Stockwell makes up for this overdose of biochemistry lingo with communicating very well the relevance of basic research and the power of the scientific method.

I'd give this book four out of five stars because I appreciate Stockwell has taken the time to write it to begin with.

Condensed penguins

[Img: Antarctic Connection]

During my time in Canada, the coldest temperature I recall reading off the digital display on the way back home was -28°C. I couldn't help asking myself why did humans ever settle in such hostile environment (and wtf was I doing there). But if you think Canadians are though (and Germans wimps), hear the story of the Emperor Penguin (Aptenodytes forsteri), that lives in Antarctica.

The Emperor Penguin's adaption to the cold, which can drop down to -50°C during the Antarctic winter, is plainly amazing. Feathers, fat, and their ability to increase the metabolism rate at low temperatures allow the penguins to survive. Equally amazing, but also bizarre, is the Emperor Penguin's breeding behavior.

Penguin colonies up to some thousands have nesting areas inland that are, depending on the annual ice thickness, 50-120 km away from the edge of the pack ice. At the beginning of the Antarctic Winter, some time in March or April, the penguins get out of the water and travel to their nesting areas, mostly walking or sliding on the ice. After mating, the female lays a single egg in late May or early June and passes it on to the male for incubation while she walks back to the shore.

In an environment of ice, snow, and the occasional rock the penguins can't build nests, so they balance the egg on their feet in their brood pouch. And, since there isn't much fish to find on the pack ice, they don't eat. Yes, you read that correctly: They walk a hundred kilometers, the female lays an egg and walks back a hundred kilometers, while the male sits on the egg for another 2 months, during the Antarctic Winter, in the dark, without the female, and all that without eating a thing. By the time the egg hatches, the male has fasted for almost 4 months, lost half of his body weight, and hopes for the female to return because he has nothing to feed the chick. And then he still has to walk back to the shore so he doesn't starve. But hey, my husband assembled the baby cribs!

There's a great documentary, "The March of the Penguins," telling this story:



But the penguins know some physics too!

While a single penguin is able to maintain its core body temperature in the freezing cold, this costs a lot of energy which he can't afford during his Winter fast. So what the Emperor penguins do is they form huddles. The density of the huddles increases with falling air temperature. If the huddle gets very dense, the penguins are in a nearly hexagonal arrangement. In a study from about a decade ago, researchers glued measuring devices to some penguin's lower back. They found that the temperature inside huddles can reach as much as 37.5° (Gilbert et al, arXiv:q-bio/0701051v1 [q-bio.PE]).

The penguins in these huddles do not stand still, but they move in occasional small steps which have recently been subject of another study (Zitterbart et al, PLoS ONE 6(6): e20260). The researchers shot movies of the penguin huddles and tracked the position of the birds. As you will easily notice if you read the paper, David Zitterbart is a condensed matter physicist who compares the huddling penguins to particles with an attractive interaction and the tight huddling to a jamming transition in granular materials. Just that the penguins manage to prevent jamming by coordinated movements. The little steps of the penguins propagate through the huddle like density waves. They measured densities up to 21 birds per square meter.

According to their paper, the penguins' little steps have a three-fold benefit. One is that they help the packing to get denser, much the same way like tapping a bag with ground coffee. The second is that they move the whole huddle, allowing huddles to merge and adjust position and direction. The third one is a turnover of penguins in the huddle, moving those from the outside towards the warmer inside. Though one might argue that what actually is responsible for the turnover is not the little forward steps, but the penguins on the front leaving the huddle and joining it (or another huddle) on the back. But without the forward steps, the turnover would make the huddle move backward.

The below movie from Zitterbart et al's paper (Yes, we live in the age of Harry Potter, where paper has moving pictures!) shows a time lapse of the penguin huddling (actual time about 1h):



I was very confused about the penguin turnover because in all the Emperor Penguin huddles in "The March of the Penguin" and photos I had seen only penguin backs and could not for the hell of it figure out where the penguins are supposed to go if they are all facing towards each other. So I wrote an email to David Zitterbart who kindly explained that there's two different kind of huddles that have been observed. Those that they've described in their paper, which have a forward direction, and circular ones that I had seen images of. He writes that no one really knows how the circular ones work, but they hope to find out with the next experiment.