The last lab rat has eight arms

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Just after a squid leaflet, on the ground floor of a brick building of the Marine Biology Laboratory (MBL) in Woods Hole, Mass., A handful of people in white coats flicker between rows tanks the size of a microwave. They monitor water quality, manage food, take notes, and otherwise transform the landscape of marine biology research.

Led by squirrel magician Bret Grasse, MBL's Marine Resource Center workers are trying to master the science of raising cephalopods – a group of squid, cuttlefish and octopus – in captivity. A steady stream of fresh Cape Cod seawater coming from an adjacent inlet flows through a network of pipes, creating an impression of chaos in the wet, vast but tight laboratory. As my tour continues, the order emerges. What originally looks like improperly placed plastic bottles inside some tanks turns out to be old bottles of Coca-Cola deliberately placed in the middle of the tank to incubate cephalopod eggs. The air injected into each bottle keeps translucent eggs the size of a dry grape swinging inside. Some cephalopod parents oxygenate their eggs until hatching, but Grasse has developed the soda bottle incubator to automate the task, releasing parents for the production of the next batch of eggs. eggs. This is one of the many low-tech innovations that the team has implemented to mass-produce cephalopods used as laboratory animals. If they succeed, they will have contributed to the inauguration of the last marine model organization in the world.

A model organism is used as a test system to reveal universal truths of biology. The model may represent a larger group of animals or serve as an indirect indicator for humans or other species. Much of our knowledge about the development of living organisms, including genetics, stems from research on a handful of model organisms such as fruit flies, roundworms, zebrafish, mice and rats. They are small, short-lived animals that are easy to keep and reproduce. We can easily analyze and modify genomes to study the interactions between genetics, biology and diseases, and then try to apply that knowledge to humans.

Scientists already have access to other marine animals for their laboratory work and have used them to discover discoveries in all subjects, from nerve transmission to fertilization, through the mechanisms of learning and memory. . But since the scientific community has adopted the study of genetics over the past three decades, its need for new genetically manipulable marine models, that is to say laboratory animals with easily manipulated genes, became obvious. MBL wants to fill the gap by producing the first genetically manipulable cephalopod model organism in the world.

Regarding what we could learn from cephalopods, opportunities abound.

Caroline Albertin, cephalopod biologist at MBL, explains Caroline Albertin, a scientist who organizes animals in about 35 phylas, leaving gaping holes in our biological knowledge. It's like wanting to understand human physiology, but never studying men.

"We do not have access to large parts of the biological world," says Albertin. In 2015, she was part of the first team to sequence an octopus genome. Cephalopods have a lot in common with vertebrates, she says – "things like big brains, camera eyes and a closed circulatory system" – but they have evolved completely independently. "They are very close to other molluscs, like snails and clams, which do not have these characteristics," she adds.

The study of cephalopod genes and their embryology – the way these genes are deployed during development – could help us to improve our knowledge about the evolution and biology of the body. As Albertin points out, studying the nuances of the extended nervous system of cephalopods could lead to a better understanding of the human brain. And discovering how cephalopods regenerate their arms, despite the presence of large nerve cords, could make a breakthrough in the treatment of spinal cord injuries.

Other cephalopod experts, such as the neuromolecular biologist, Josh Rosenthal, who oversees the project of developing model organism cephalopods at MBL, are excited about the prospects of studying additional innovations brought about by cephalopods, such as their ability to modify their own genetic information. The three hearts of cephalopods and their ability to match the color, pattern and shape of their environment also fascinate biologists in the hope of discovering the underlying biological principles of these characters.

But before MBL can build momentum around cephalopod research, scientists must first master the art of keeping their subjects uncomfortable and mass producing in captivity; which is much more delicate with cephalopods than with mice.

MBL, a subsidiary of the University of Chicago, is proud to study nature through a hands-on approach rather than through books. A few years ago, a group of researchers from the nonprofit corporation began discussions on the development of a new model marine species with a treatable genetic system. The proximity of MBL with a rich part of the ocean, where the tropical waters brought by the Gulf Stream meet the cold waters of the North Atlantic, has helped to make it a world center for marine research. Dozens of students and scientists come to training and research each summer, creating a palpable atmosphere of enthusiasm for discovering the mysteries of nature. The researchers knew that any new body model they developed here would likely quickly be adopted by visiting scientists who would bring new ideas and techniques to their original labs.

The group finally agreed on the cephalopods and in April 2017, MBL started work to concretize a new model species. One of the first calls was in Grasse.

With his laid-back style, the aquarist Grasse exudes a surfer atmosphere on the west coast as he pauses between tanks to talk about great biology ideas and small modifications to his aquarium. In his last job as a Senior Outgrower at the Monterey Bay Aquarium in California, he designed and developed the first large-scale public exhibition on cephalopods in the world. "Out of two species that we exhibited, there were probably four more behind the scenes with which we were doing things," he says. "I have many years of innovative, hands-on, practical experience to address different challenges in cephalopod farming." The MBL cephalopod project now leverages this expertise to make it a success.

MBL, who has a long and venerable history of research on cephalopods, already had a collection of live cephalopods, mainly squid and cuttlefish caught in the wild or donated by other laboratories. In addition, the organization had experience in raising cephalopods on a smaller scale, which gave it a good start. But to become a reliable source of cephalopods, MBL expects to have to continuously produce a large number of these animals – hundreds, thousands, or more – to support the larger scientific community with ready-made model organisms. to be shipped.

According to Grasse, to successfully breed such notoriously difficult animals, one must learn to read their subtle signals, such as a slight change in the coloring of their skin or a minor change in behavior. "The way they breathe, swim, siphon or show on top of each other will give me clues as to what they need and allow me to respond proactively."

There is also a need to work tirelessly to maintain the life-stage conditions of a cephalopod (food, habitat, societal, and water quality considerations) and to get better results. Most cephalopod species of MBL have a natural longevity of six months to one year and reach sexual maturity at three months. "They live fast, die young," says Grasse. His group's work has already increased longevity beyond normal life in the wild and has raised the egg survival rate to 90% or higher for some species.

By combining the Grasse experiment with the requirements of scientists, the MBL team has targeted several species that meet some important criteria for potential model organisms: animals are small, have short lifespan and maintain cycles of growth. predictable reproduction. Highlights include Hawaiian squid, California's two-branched octopus, flaming cuttlefish, striped striped squid and dwarf cuttlefish. Pygmy zebra octopus is a more recent addition to the list. Scientists are trying to raise the animal the size of a diamond in captivity since the 1970s and, by the end of 2018, MBL has become the first to breed for several generations, says Grasse . The list could be further reduced depending on the reproductive quality of each species, or we could end up with many of these species as new laboratory organisms.

It's a great strategy to select some representative cephalopods and focus our efforts on understanding them, says Jennifer Mather, cephalopod researcher at the University of Lethbridge in Alberta, who is not involved in the project. "We know too little about these animals, including on such fundamental aspects of their lives as behavior and ecology."

The ultimate goal of the MBL's cephalopod team is to supply all selected species at different stages of their lives, so that they can immediately respond to requests from scientists around the world. "So, according to the scientific question, researchers can have exactly the type of resources they need and want," says Grasse. Prior to the cephalopod program, MBL had perhaps 50 cuttlefish and 30 squid and now has some 4,000 cephalopods, almost all grown in culture.

While the Grasse crew finds the best methodologies for culturing cephalopods, the Rosenthal geneticist team at MBL is also immersed in the other half of the equation: dive deep into the genes of their test subjects. Once the cephalopods have been regularly stocked and the sequencing and cataloging of the genomes is complete, they plan to start manipulating the DNA of some broods to provide more options for future clients. . Scientists may wish to order cephalopods with some added or deleted genes to study a particular problem, for example. Part of the job of geneticists is to develop a scientific technique that will allow researchers to make these changes. Many of the ideas that scientists hope to obtain from cephalopods will depend on their ability to manipulate genes one by one, often in the embryonic stage, and then to study the impact on the animal, Rosenthal explains.

Once scientists have successfully modified a gene, they must be able to keep the animal alive, growing and breeding to see if genetic change is evident over successive generations, adds Rosenthal. "Cultivating them is the key." External researchers could educate MBL cephalopods in their own laboratories if they had the skills or work on the MBL site for a while with the help of the cephalopod team.

The benefits of the project for MBL are clear: the prestige associated with the leading position and the sole source of one of the few genetically manipulable model organisms in the world – although researchers say that prestige is not their main motivation – and that there is potential for financial gain.

For the moment, the cephalopods and lessons that Grasse and his team have learned by breeding them are freely available to other scientists wishing to do research at MBL. If the project succeeds, it will also be easier for MBL to attract more scientists to work here in the laboratory, not just during the idyllic summer months, when Woods Hole will become the perfect image, with floating cabins on the calm waters of the bay. Seagulls sliding along boats and families strolling on a sunny walk.

Those who want to bring back cephalopods to their laboratory will have to pay. MBL has already started selling some of their animals to external researchers to help cover project costs while staff scientists are continuing development work but are not making a profit yet. Cephalopod embryos can be sold for 5 USD, adults 25 USD to 300 USD. "We are not trying to get rich; Our short-term goal is to encourage science and research, as well as the use of these animals, "Grasse said. "If we all continue to use exactly the same models, the same fruit flies, the same zebrafish … if we continue to ask the same animals, we can only go very far. It is up to us, the scientific culture, to expand a little. "

The cephalopod project is based on the understanding that the scientific community Needs new laboratory animals. But I leave the Grasse laboratory in conflict over whether MBL should pursue cephalopods as model organisms, given the seemingly intelligent and charismatic nature of these creatures.

Before my tour with Grasse, I met Roger Hanlon, senior scientist at MBL and world expert cephalopods. He explained that it seems that some cephalopods have an episodic memory, able to remember the what, where and when of an event, sign of high cognitive abilities compared to many vertebrates. The complexity and speed of the camouflage behavior of a cephalopod is also impressive.

Because of the complexity of their brains, cephalopods are protected by the laboratory animal laws of Canada, the European Union, New Zealand and certain Australian states. Researchers in these locations must obtain ethical approval for their studies and treat animals with humanity. But there is no such regulation in the United States. While some critics oppose any experimentation on cephalopods, most of the scientists I've talked to, including Hanlon, say that as long as cephalopods are kept in good conditions of well-being, it is ethical to continue such work.

Before leaving the Marine Resource Center, I spend a moment alone in a corner of the building housing piles of mini aquariums, like a sort of cuttlefish condo, and take a look at one of them. A couple of cuttlefish hover in the middle of the aquarium like an alien spacecraft, staring at their big eyes, student back. I would like to be able to read their thoughts and tell the story from their point of view.