From The Wyss Institute (US): “Team builds first living robots that can reproduce” 

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Wyss Institute bloc
From The Wyss Institute (US)

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Harvard University (US)

November 29, 2021
Joshua Brown, The University of Vermont (US) Communications

AI-designed Xenobots reveal entirely new form of biological self-replication—promising for regenerative medicine.

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AI-designed (C-shaped) organisms push loose stem cells (white) into piles as they move through their environment. Credit: Douglas Blackiston and Sam Kriegman.

To persist, life must reproduce. Over billions of years, organisms have evolved many ways of replicating, from budding plants to sexual animals to invading viruses.

Now scientists at The University of Vermont (US), Tufts University (US), and the Wyss Institute for Biologically Inspired Engineering at Harvard University have discovered an entirely new form of biological reproduction—and applied their discovery to create the first-ever, self-replicating living robots.

The same team that built the first living robots (“Xenobots,” assembled from frog cells—reported in 2020) [PNAS] has discovered that these computer-designed and hand-assembled organisms can swim out into their tiny dish, find single cells, gather hundreds of them together, and assemble “baby” Xenobots inside their Pac-Man-shaped “mouth”—that, a few days later, become new Xenobots that look and move just like themselves.

And then these new Xenobots can go out find cells and build copies of themselves. Again and again.

“With the right design—they will spontaneously self-replicate,” says Joshua Bongard, Ph.D., a computer scientist and robotics expert at the University of Vermont who co-led the new research.

The results of the new research were published November 29, 2021, in the PNAS.

Into the Unknown

In a Xenopus laevis frog, these embryonic cells would develop into skin. “They would be sitting on the outside of a tadpole, keeping out pathogens and redistributing mucus,” says Michael Levin, Ph.D., a professor of biology and director of the Allen Discovery Center at Tufts University and co-leader of the new research. “But we’re putting them into a novel context. We’re giving them a chance to reimagine their multicellularity.” Levin is also an Associate Faculty member at the Wyss Institute.

And what they imagine is something far different than skin. “People have thought for quite a long time that we’ve worked out all the ways that life can reproduce or replicate. But this is something that’s never been observed before,” says co-author Douglas Blackiston, Ph.D., the senior scientist at Tufts University and the Wyss Institute who assembled the Xenobot “parents” and developed the biological portion of the new study.

“This is profound,” says Levin. “These cells have the genome of a frog, but, freed from becoming tadpoles, they use their collective intelligence, a plasticity, to do something astounding.” In earlier experiments, the scientists were amazed that Xenobots could be designed to achieve simple tasks. Now they are stunned that these biological objects—a computer-designed collection of cells—will spontaneously replicate. “We have the full, unaltered frog genome,” says Levin, “but it gave no hint that these cells can work together on this new task,” of gathering and then compressing separated cells into working self-copies.

“These are frog cells replicating in a way that is very different from how frogs do it. No animal or plant known to science replicates in this way,” says Sam Kriegman, Ph.D., the lead author on the new study, who completed his Ph.D. in Bongard’s lab at UVM and is now a post-doctoral researcher at Tuft’s Allen Center and Harvard University’s Wyss Institute for Biologically Inspired Engineering.

On its own the Xenobot parent made of some 3000 cells forms a sphere. “These can make children but then the system normally dies out after that. It’s very hard actually to get the system to keep reproducing,” says Kriegman. But with an artificial intelligence program working on the Deep Green supercomputer cluster at UVM’s Vermont Advanced Computing Core, an evolutionary algorithm was able to test billions of body shapes in simulation—triangles, squares, pyramids, starfish—to find ones that allowed the cells to be more effective at the motion-based “kinematic” replication reported in the new research.

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Deep Green supercomputer at The University of Vermont (US).

“We asked the supercomputer at UVM to figure out how to adjust the shape of the initial parents, and the AI came up with some strange designs after months of chugging away including one that resembled Pac-Man,” says Kriegman. “It’s very non-intuitive. It looks very simple, but it’s not something a human engineer would come up with. Why one tiny mouth? Why not five? We sent the results to Doug and he built these Pac-Man-shaped parent Xenobots. Then those parents built children, who built grandchildren, who built great-grandchildren, who built great-great-grandchildren.” In other words, the right design greatly extended the number of generations.

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An AI-designed “parent” organism (C shape; red) beside stem cells that have been compressed into a ball (“offspring”; green). Credit: Douglas Blackiston and Sam Kriegman.

Kinematic replication is well-known at the level of molecules—but it has never been observed before at the scale of whole cells or organisms.

“We’ve discovered that there is this previously unknown space within organisms, or living systems, and it’s a vast space,” says Bongard. “How do we then go about exploring that space? We found Xenobots that walk. We found Xenobots that swim. And now, in this study, we’ve found Xenobots that kinematically replicate. What else is out there?”

Or, as the scientists write in the PNAS study: “life harbors surprising behaviors just below the surface, waiting to be uncovered.”

Responding to Risk

Some people may find this exhilarating. Others may react with concern, or even terror, to the notion of a self-replicating biotechnology. For the team of scientists, the goal is deeper understanding.

“We are working to understand this property: replication. The world and technologies are rapidly changing. It’s important, for society as a whole, that we study and understand how this works,” says Bongard. These millimeter-sized living machines, entirely contained in a laboratory, easily extinguished, and vetted by federal, state and institutional ethics experts, “are not what keep me awake at night. What presents risk is the next pandemic; accelerating ecosystem damage from pollution; intensifying threats from climate change,” says UVM’s Bongard. “This is an ideal system in which to study self-replicating systems. We have a moral imperative to understand the conditions under which we can control it, direct it, douse it, exaggerate it.”

Bongard points to the COVID epidemic and the hunt for a vaccine. “The speed at which we can produce solutions matters deeply. If we can develop technologies, learning from Xenobots, where we can quickly tell the AI: ‘We need a biological tool that does X and Y and suppresses Z,’ —that could be very beneficial. Today, that takes an exceedingly long time.” The team aims to accelerate how quickly people can go from identifying a problem to generating solutions—”like deploying living machines to pull microplastics out of waterways or build new medicines,” Bongard says.

“We need to create technological solutions that grow at the same rate as the challenges we face,” Bongard says.

And the team sees promise in the research for advancements toward regenerative medicine. “If we knew how to tell collections of cells to do what we wanted them to do, ultimately, that’s regenerative medicine—that’s the solution to traumatic injury, birth defects, cancer, and aging,” says Levin. “All of these different problems are here because we don’t know how to predict and control what groups of cells are going to build. Xenobots are a new platform for teaching us.”

See the full article here .

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Wyss Institute campus

The Wyss (pronounced “Veese”) Institute (US) for Biologically Inspired Engineering uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world.

Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs.

Harvard University campus

Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Established in 1636 and named for its first benefactor, clergyman John Harvard, Harvard is the oldest institution of higher learning in the United States and among the most prestigious in the world.
The Massachusetts colonial legislature, the General Court, authorized Harvard’s founding. In its early years, Harvard College primarily trained Congregational and Unitarian clergy, although it has never been formally affiliated with any denomination. Its curriculum and student body were gradually secularized during the 18th century, and by the 19th century, Harvard had emerged as the central cultural establishment among the Boston elite. Following the American Civil War, President Charles William Eliot’s long tenure (1869–1909) transformed the college and affiliated professional schools into a modern research university; Harvard became a founding member of the Association of American Universities in 1900.[10] James B. Conant led the university through the Great Depression and World War II; he liberalized admissions after the war.
The university is composed of ten academic faculties plus the Radcliffe Institute for Advanced Study. Arts and Sciences offers study in a wide range of academic disciplines for undergraduates and for graduates, while the other faculties offer only graduate degrees, mostly professional. Harvard has three main campuses: the 209-acre (85 ha) Cambridge campus centered on Harvard Yard; an adjoining campus immediately across the Charles River in the Allston neighborhood of Boston; and the medical campus in Boston’s Longwood Medical Area. Harvard’s endowment is valued at $41.9 billion, making it the largest of any academic institution. Endowment income helps enable the undergraduate college to admit students regardless of financial need and provide generous financial aid with no loans The Harvard Library is the world’s largest academic library system, comprising 79 individual libraries holding about 20.4 million items.
Harvard has more alumni, faculty, and researchers who have won Nobel Prizes (161) and Fields Medals (18) than any other university in the world and more alumni who have been members of the U.S. Congress, MacArthur Fellows, Rhodes Scholars (375), and Marshall Scholars (255) than any other university in the United States. Its alumni also include eight U.S. presidents and 188 living billionaires, the most of any university. Fourteen Turing Award laureates have been Harvard affiliates. Students and alumni have also won 10 Academy Awards, 48 Pulitzer Prizes, and 108 Olympic medals (46 gold), and they have founded many notable companies.
Colonial
Harvard was established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. In 1638, it acquired British North America’s first known printing press. In 1639, it was named Harvard College after deceased clergyman John Harvard, an alumnus of the University of Cambridge(UK) who had left the school £779 and his library of some 400 volumes.[22] The charter creating the Harvard Corporation was granted in 1650.
A 1643 publication gave the school’s purpose as “to advance learning and perpetuate it to posterity, dreading to leave an illiterate ministry to the churches when our present ministers shall lie in the dust.” It trained many Puritan ministers in its early years and offered a classic curriculum based on the English university model—many leaders in the colony had attended the University of Cambridge—but conformed to the tenets of Puritanism. Harvard has never affiliated with any particular denomination, though many of its earliest graduates went on to become clergymen in Congregational and Unitarian churches.
Increase Mather served as president from 1681 to 1701. In 1708, John Leverett became the first president who was not also a clergyman, marking a turning of the college away from Puritanism and toward intellectual independence.
19th century
In the 19th century, Enlightenment ideas of reason and free will were widespread among Congregational ministers, putting those ministers and their congregations in tension with more traditionalist, Calvinist parties. When Hollis Professor of Divinity David Tappan died in 1803 and President Joseph Willard died a year later, a struggle broke out over their replacements. Henry Ware was elected to the Hollis chair in 1805, and the liberal Samuel Webber was appointed to the presidency two years later, signaling the shift from the dominance of traditional ideas at Harvard to the dominance of liberal, Arminian ideas.
Charles William Eliot, president 1869–1909, eliminated the favored position of Christianity from the curriculum while opening it to student self-direction. Though Eliot was the crucial figure in the secularization of American higher education, he was motivated not by a desire to secularize education but by Transcendentalist Unitarian convictions influenced by William Ellery Channing and Ralph Waldo Emerson.
20th century
In the 20th century, Harvard’s reputation grew as a burgeoning endowment and prominent professors expanded the university’s scope. Rapid enrollment growth continued as new graduate schools were begun and the undergraduate college expanded. Radcliffe College, established in 1879 as the female counterpart of Harvard College, became one of the most prominent schools for women in the United States. Harvard became a founding member of the Association of American Universities in 1900.
The student body in the early decades of the century was predominantly “old-stock, high-status Protestants, especially Episcopalians, Congregationalists, and Presbyterians.” A 1923 proposal by President A. Lawrence Lowell that Jews be limited to 15% of undergraduates was rejected, but Lowell did ban blacks from freshman dormitories.
President James B. Conant reinvigorated creative scholarship to guarantee Harvard’s preeminence among research institutions. He saw higher education as a vehicle of opportunity for the talented rather than an entitlement for the wealthy, so Conant devised programs to identify, recruit, and support talented youth. In 1943, he asked the faculty to make a definitive statement about what general education ought to be, at the secondary as well as at the college level. The resulting Report, published in 1945, was one of the most influential manifestos in 20th century American education.

Between 1945 and 1960, admissions were opened up to bring in a more diverse group of students. No longer drawing mostly from select New England prep schools, the undergraduate college became accessible to striving middle class students from public schools; many more Jews and Catholics were admitted, but few blacks, Hispanics, or Asians. Throughout the rest of the 20th century, Harvard became more diverse.
Harvard’s graduate schools began admitting women in small numbers in the late 19th century. During World War II, students at Radcliffe College (which since 1879 had been paying Harvard professors to repeat their lectures for women) began attending Harvard classes alongside men. Women were first admitted to the medical school in 1945. Since 1971, Harvard has controlled essentially all aspects of undergraduate admission, instruction, and housing for Radcliffe women. In 1999, Radcliffe was formally merged into Harvard.
21st century
Drew Gilpin Faust, previously the dean of the Radcliffe Institute for Advanced Study, became Harvard’s first woman president on July 1, 2007. She was succeeded by Lawrence Bacow on July 1, 2018.
Research
Harvard is a founding member of the Association of American Universities and a preeminent research university with “very high” research activity (R1) and comprehensive doctoral programs across the arts, sciences, engineering, and medicine according to the Carnegie Classification.
With the medical school consistently ranking first among medical schools for research, biomedical research is an area of particular strength for the university. More than 11,000 faculty and over 1,600 graduate students conduct research at the medical school as well as its 15 affiliated hospitals and research institutes. The medical school and its affiliates attracted $1.65 billion in competitive research grants from the National Institutes of Health in 2019, more than twice as much as any other university.