How naturally-produced opioids help plumb the depths of animal minds

Amidst the ongoing debate over whether artificial intelligence is really sentient, scientists are still trying to figure out the same thing about non-human animals. Amazingly, naturally-produced painkillers have long been considered a key indicator of possible sentience in animals. America can ban all the opioids it wants, but still won’t stop your brain from making them or seeking the relief from suffering they provide, and so they have been seen as a kind of smoking gun for sentience in non-human animals as well. But a look at the evolutionary role of endorphins really highlights the complexity of conscious experience – especially our own.

The field of animal consciousness studies has grown in leaps and bounds over the past couple of decades. The clearest evidence comes from studies in neuroscience on the neurophysiological basis of behavioral responses to animals’ subjective experiences — such as a dog seeking to relieve its thirst by drinking — definitively overturns the legacy of mid-20th Century behaviorism, in which animals were considered to have a set of automatic behaviors that nevertheless didn’t reflect a sentient mind.

“We are constantly underestimating animals,” David Mellor, a retired professor of applied physiology and bioethics, told Salon from his home in New Zealand. “Every time, we are surprised at how smart animals are. It’s because we have underestimated them, not because they’ve suddenly become smart.”

Indeed, it’s human understanding that seems to have deepened.

“It’s really only in the last fifteen years, I would say, that there’s been an attempt to integrate consciousness science with comparative psychology or comparative cognition, the study of animal minds, so that now we’re seeing the emergence of a science of animal consciousness,” Jonathan Birch, a philosopher of biological sciences at the London School of Economics, told Salon. Birch was just back in London after co-hosting a conference in April on animal consciousness in New York City that culminated in the release of a pithy but important new declaration on animal sentience by dozens of luminaries in the field.

Over those last fifteen years, the markers we look for as hints of sentience – that within their furry (or scaly, or feathery) little heads there is a quality of “what it’s like for that animal to be itself” – have grown beyond simply what we expect based on our own human or primate, or even mammal experience.

Importantly, the definition of sentience isn’t a neutral one: it is profoundly political, linked as it is to resource use and granting of rights. Once we understand a creature to be sentient, we recognize ethical imperatives. It is not so long since it was broadly believed that human infants didn’t experience pain the way older children and adults do, with babies rarely receiving anesthetics before painful procedures, their cries considered automatic and their nervous systems considered too underdeveloped to offer them a subjective experience of pain. A 1987 study of stress responses in newborns provided the first strong evidence that this was terribly wrong.

We no longer routinely deny that what looks like a behavioral response to pleasure or pain in a baby reflects its subjective sense of positive or negative feelings. And more recently, we’ve become willing to consider that other mammals and less familiar animals – crabs, say, or octopuses – really are sentient, not just seeming so. While we can consider many aspects of sentience, perhaps the most basic aspect we look for – the one that resonates most strongly, especially when we consider how sentience applies to animal rights, remains the ability to experience enjoyment and suffering, pleasure or pain.

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To apply evolving understandings of animals’ subjective experience and its relation to structure and function to animal welfare, Mellor came up with the term “welfare-aligned sentience.”

“Basically, it is that animals that can have positive and negative experiences that matter to them are sentient in a welfare-aligned sense.” he said. “Because the welfare of an animal depends on the balance of positive and negative experiences it can have at any one time or over a period.”

Evolution produced sentience

The kingdom of animals is a broad category that includes everything from mosquitos to chimpanzees. Vertebrates are a sub-group of animals with backbones, a development that emerged some 450 million years ago. Given the prevalence of back pain in at least some of their long-suffering descendants, perhaps it’s appropriate that with the first vertebrates on Earth came the first painkillers on Earth.

Of course we’re speaking about endorphins – naturally-produced opioids pumped out by the brains and spinal cord, not only those of humans but of every vertebrate. Endorphin is a portmanteau of “endogenous opioid” and in fact drugs like morphine and fentanyl only work in our bodies because they mimic the effects of these innate peptides.

Every creature with a backbone releases endorphins in response to stress. The existence of this self-made morphine has been considered a way of identifying animals – until recently, mostly just mammals – capable of experiencing pleasure and pain. In fact, RSPCA scientists argue that having such neurotransmitters constitutes one form of evidence for sentience. We understand creatures that produce their own morphine to relieve pain are creatures capable of experiencing pleasure and pain, able to suffer and for this reason – the thinking goes – entitled to not be abused or treated in such a way as to cause unnecessary pain.

Mellor further argues that in welfare-aligned sentience we might try to support animals under our care to thrive, facilitating what’s called “positive-valenced experiences” that, just like pain, also suggest that “sense of what it’s like to be oneself” — things like warmth, comfort, interest and enjoyment.

And so we can consider aspects of animal consciousness beyond the experience of suffering, such as playfulness and curiosity, the ability to make decisions, purposefulness. We’re also expanding our understanding of what sort of evidence we should be looking for.

You don’t need a backbone to be sentient

Although invertebrates do have the opioid precursor proenkephalin and some other signs of precursors to the opioids found in vertebrates like us, endorphins as we know them evolved in vertebrates. Thus opioid receptors are not found in invertebrate animals like the nematode C. elegans, the honeybee or the squid. While some research has found that morphine can have analgesic effects on crayfish, we don’t yet know what type of receptor it’s targeting, though it probably relates to these evolutionarily early starts at an opioid system.

But invertebrates like octopuses are known to be intelligent, even playful. Should their inability to produce their own opioids  preclude them from being considered sentient? Ah, but that would be applying a human bias, or rather a vertebrate bias, to our quest to understand sentience in creatures as unlike us as possible. So we need to look for other chemicals that might have evolved to fulfill analogous functions, whether the experience of suffering and its relief, or other attributes we increasingly recognize as aspects of a conscious experience.

“In terms of vertebrates, [this means] having the equivalent of a cerebral cortex. And that doesn’t mean that cephalopods and crustaceans and so on that don’t have a nervous system the same as vertebrates are not sentient,” Mellor told Salon. "The neural bundles and so on in them clearly have a capacity to motivate behaviors that are purposeful."

“We acknowledge a huge amount of uncertainty in this area,” Birch told Salon, “but also want to emphasize that despite that uncertainty, there’s quite a lot of high quality evidence for conscious experience, not just in mammals and birds, but also in fishes, reptiles, amphibians and invertebrates like octopuses, crabs, lobsters and insects. There’s at least a realistic possibility of conscious experience in all of these animals”.

It’s reasonable to expect that different aspects of sentience evolved at different points in the evolutionary tree, with divergent groups going on to develop their own ways of being conscious and having a sense of what it’s like to be themselves.

“There’s quite a lot of behaviors where if you saw them in a mammal or bird, you will quite readily accept the behavior as evidence of pain,” Birch explained. “And so it’s largely about avoiding double standards. When we’re thinking about pain in vertebrates, and invertebrates display the same markers, we should be willing to entertain the idea of pain in those animals as well.”

Once you start looking beyond just pain, where we are able to use morphine to test for the experience of pain and its relief, other neurotransmitters than endorphins can become clues to the neurophysiological bases of subjective or sentient experience. In shore crabs, for example, Prozac may calm experimentally-induced anxious behaviors. Birch also cites an experiment in which lidocaine was used to relieve experimentally-induced pain from an injection of acetic acid in an octopus.

The New York Declaration on Animal Consciousness is meant to be a conservative minimum that everyone can agree on despite the uncertainties on exactly how sentient some of these animals are. It reads in its entirety:

“Which animals have the capacity for conscious experience? While much uncertainty remains, some points of wide agreement have emerged.

First, there is strong scientific support for attributions of conscious experience to other mammals and to birds.

Second, the empirical evidence indicates at least a realistic possibility of conscious experience in all vertebrates (including reptiles, amphibians, and fishes) and many invertebrates (including, at minimum, cephalopod mollusks, decapod crustaceans, and insects).

Third, when there is a realistic possibility of conscious experience in an animal, it is irresponsible to ignore that possibility in decisions affecting that animal. We should consider welfare risks and use the evidence to inform our responses to these risks.”

Seeking evidence where we find it

Rather than moving from a purely behaviorist approach to a purely neurochemical one, the current thinking is that we should evaluate possible consciousness with an open mind, and in fact seek out evidence for sentience, correcting for our own anthropic or perhaps vertebrate biases by combining evidence in the form of behaviors that, if we did them, we would attribute sentience to them, and in the form of neurotransmitters and neural structures analogous to those that allow us to, well, experience our own experiences.

If you give honeybees a vigorous sixty-second shaking, mimicking an attack on their hive, they can develop pessimistic cognitive biases: coming to expect the worst. As with humans, crayfish and capybaras, if you look you’ll find the biochemical markers of the poor bees’ cognitive change. In this case, a reduction of the chemical messengers dopamine, octopamine (a chemical analogous to the norepinephrine that has largely replaced its function in vertebrates), and serotonin in their hemolymph, the invertebrate equivalent of blood.

If we are willing to entertain the notion of sentience in bees, where will this end? A new pre-print atlas of neurotransmitters maps out such chemicals in C. elegans, a millimeter-long multicellular roundworm often used in biological experiments. Are we positing sentience in this little nematode? Not yet. And it doesn’t seem equipped to feel pain with opioid receptors, though like other invertebrates, it may have that very primitive opioid system.

But with familiar neurochemicals like glutamate, acetylcholine, GABA, serotonin, tyramine and octopamine zipping around its primitive nervous system, it’s worth paying close attention to its behavior, too, so we can do our best to help all our animal relations thrive.