Play God!
Posted on 06/23/2006 12:06:08 PM PDT by LibWhacker
Mark Bedau ’76 and Norman Packard ’77 used to stay up late nights at Reed pondering the nature of life. What makes organisms alive? Is there a knowable organizing principle behind living cells? Can life be broken down into its constituent parts?
Thirty years later, Bedau and Packard are on a quest for answers. Surrounded by powerful computers and sophisticated equipment in a high-tech industrial park on the outskirts of Venice, Italy—and bankrolled with millions of euros—they are trying to produce actual cells. The two Reedies are part of a long-shot entry in the race to create artificial life.
Bedau, a philosophy professor at Reed, and Packard, a physicist known for his entrepreneurial success at applying computer models to predict financial markets, are the founders of ProtoLife, an eight-employee biotech startup. ProtoLife is in turn part of a multi-national research consortium funded by a four-year, $10 million grant from the European Commission. A steady stream of Reedies have been involved in the work of Bedau and Packard over the years, contributing to every aspect from computer simulation to bioethics research (see Reedies on the Artificial Life Trail).
Bedau, who is on leave from Reed this spring, believes that the surest way to resolve life’s basic questions is by building a basic life form from scratch. It may sound futuristic and even quixotic, but his is only one of several well-funded research groups vying to create an artificial cell capable of living off its surroundings, multiplying, and evolving.
“It’s a problem that clearly has a solution,” he says without a hint of hubris, adding that the stakes are anything but purely philosophical. Sooner or later, he predicts, powerful new technologies will create programmable living microscopic entities that can perform any number of tasks: clearing artery-clogging plaque in patients prone to heart attack, digesting toxic pollutants that are lethal to natural forms of life, or splitting water molecules to make hydrogen fuel. “It would open the door to a whole new range of technological applications, because life is incredibly flexible, adaptive, evolving, and capable of repairing itself,” Bedau says.
In fact, as Packard likes to point out, even the simplest bacteria can reproduce themselves, a capability far beyond the most advanced human-engineered computer or spacecraft. Which is one key reason Packard has invested a few million dollars of his own money in what he elegantly refers to as “crossing the barrier of nonliving matter to living matter.”
And although Packard readily acknowledges that the capabilities of artificial cells will initially fall short of even the simplest existing organisms, that doesn’t dampen his enthusiasm. “Even very simple functionality may be extremely powerful,” he says, “just by virtue of the fact that life itself is very powerful.”
Many scientists agree that advances in chemistry and biology have put the creation of a simple life form from non-living chemicals within reach; a few are convinced the goal can be attained in a decade or less. The contenders are pursuing many different approaches. But Bedau, Packard, and their colleagues at ProtoLife in Venice have embraced what is arguably the most radical and difficult route, a long-shot effort that could, if successful, redefine what it means to be alive.
Making Life’s Building Blocks
Attempts at home-brewing life have come a long way since 1953, when chemist Stanley Miller earned a permanent place in biology textbooks with his demonstration that a mixture of water, methane, and ammonia could spontaneously form some of the basic building blocks of life. All it took was a jolt of electricity.
But a primordial soup of organic compounds is not even close to being alive by anyone’s definition. In recent years, scientists have engineered entities that satisfy some of the basic criteria for defining a life form: it must be able to regenerate itself by harvesting material and energy from its surroundings; it must be able to reproduce; and it must be able to evolve.
Biologists and chemists have now generated a menagerie of microscopic entities capable of such life-like feats as spontaneously growing and dividing. In one landmark experiment in 2004, researchers at The Rockefeller University inserted protein-making components into lifeless vesicles made of fatty acids, enabling them to take in nutrients and produce proteins for up to four days before “dying.” And scientists have amassed tremendous knowledge about DNA, RNA, and similar molecules that can store information to be passed on to offspring.
The grand challenge is getting the necessary functions to work together. “Life requires self-maintenance, self-reproduction, evolvability,” Packard explained at a scientific conference in October 2005. “Each component has been well-studied in and of itself. But putting them together so that they work in concert in a way that allows objects to reproduce is not understood at all.”
Nevertheless, he and Bedau are confident that it can be done within a decade. Their competitors agree. “I do think it is possible, although many challenges remain,” says Jack Szostak of Harvard University.
Bedau and Packard believe that they have an edge with an approach that harnesses the creative power of evolution. In Venice, ProtoLife’s chief chemist, Martin Hanczyc, is focusing on finding the right mixture of materials to form membranes to contain an artificial cell. The team has collected hundreds of likely starting chemicals, including fatty acids that comprise a class known as amphiphiles, which have parts that repel water and other parts that cling to it. This gives them the curious ability to self-assemble into tiny bubbles called vesicles.
Combining different mixtures of these molecules, the researchers are generating populations of vesicles and subjecting them to a survival-of-the-fittest winnowing. Much of the lab work consists of developing methods to screen large numbers of vesicles quickly for size, strength, and other properties. The goal is to evolve structures over many generations that have never arisen in nature or via human engineering.
It’s familiar territory for Packard, who has been interested since his graduate school days at UC Santa Cruz in the fields of machine learning and evolution. “Now, we’re using evolutionary methods in machine learning to explore these [new] biological systems,” he explains. “That’s a new frontier in biochemistry and molecular biology, and we’re finding ourselves in the middle of it.”
Bedau, meanwhile, has spent 15 years studying the way natural organisms and other systems evolve, and he’s developed statistical models to track the process of evolution. He’s adapting these to detect subtle advantages in components of would-be life forms. “Critics call it ‘irrational design,’” Bedau says, referring to the rational design process in which chemists engineer compounds to fit a pre-ordained shape. “We call it evolutionary design.”
And since the ProtoLife scientists are starting from scratch, almost anything goes. For instance, while most living cells conform to a limited size range, the scientists can make them radically smaller. Instead of DNA, they are open to using any information-encoding molecule that might work. Steen Rasmussen, a colleague who works at Los Alamos National Laboratory, has developed plans for an artificial cell literally turned inside out: It bears its genes and metabolic machinery on its outer membrane.
Another key part of their effort is to develop microscopic life-support systems for artificial cells. Chemist John McCaskill at Ruhr University in Germany is developing computer-controlled microscopic devices to control the flow of nutrients to artificial cells. The researchers plan to wean their creations from life-support systems one step at a time as the successive generations become more capable of independence.
Tangles with Teleology
Concocting life in a laboratory is not exactly typical work for a philosopher and a physicist. But it was a logical step in the journey Bedau and Packard began as students at Reed.
In graduate school and beyond, Packard became an expert in chaos theory, complex systems, and computer simulation. After a stint teaching physics at the University of Illinois, he and two partners founded the Prediction Company in Santa Fe in 1991 to provide financial firms with sophisticated automated systems in arenas such as derivatives trading. The company made a big splash and was purchased by Swiss investment bank UBS for an undisclosed sum in 2005 (The Predictors: How a Band of Maverick Physicists Used Chaos Theory to Trade Their Way to a Fortune on Wall Street, by Thomas A. Bass, chronicles the Prediction Company’s success).
In philosophy, meanwhile, Bedau was tangling with problems of teleology, seeking to explain the goal-directedness, or purpose, of living things. He went on to become editor of the journal Artificial Life and organized a conference on the topic in 2000 at Reed.
By then, the two Reedies were looking for bigger challenges.They started meeting with McCaskill and Rasmussen, both of whom were already working in the field. The group chose inspirational settings: Bedau’s favorite swimming hole on the Wilson River in Oregon’s Coast Range; Cannobio, Italy, on the banks of Lago Maggiore in the Italian Alps (Packard’s wife, Grazia Peduzzi, is from nearby Milan); Ghost Ranch in New Mexico, where the group hiked in the moonlight to the top of Petranos Peak.
And that’s where they hatched the idea of shifting from theories and computer simulations to experiments and real-world applications. “It would be absolutely concrete and real, in test tubes—not just theories, even though all of our backgrounds were in theory,” Bedau remembers thinking.
The European Commission liked their ideas enough to award a grant totaling $10.5 million to a project the four developed with several other partners in 2004. Called “Programmable Artificial Cell Evolution,” or PACE, it now includes a dozen partners and cooperating groups from across Europe, as well as three from the United States: Reed College, Los Alamos National Laboratory, and Argonne National Laboratory.
Top-down or bottom-up?
Some skeptics doubt whether the efforts of ProtoLife and its collaborators will produce anything useful. Among them are molecular biologists who point out that billions of years of evolution have gone into the current design of natural organisms. “To pretend to do life with simple chemistry is a nice ambitious idea,” biochemist Pier Luigi Luisi of the University of Rome told the journal New Scientist. “But it’s probably not going to be very efficient.”
In contrast to ProtoLife’s “bottom-up” approach of trying to create living cells from scratch, some researchers are trying to exploit the capabilities of existing cells. Their method involves retrofitting naturally occurring bacteria, and stripping out components to find the minimal set required for life. Among those pursuing this “top-down” approach is genome-sequencing pioneer J. Craig Venter, whose self-named institute is attempting to develop a basic cell to serve as a platform for adding on useful functions, such as genetic instructions for producing biofuels or drug compounds that are difficult to synthesize in the laboratory.
Szostak, the Harvard scientist, is leading an effort that borrows one of the information-conveying molecules used by living cells in nature: RNA. Szostak’s lab hopes to equip artificial cells with an RNA genome capable of self-replication.
Packard, Bedau, McCaskill, and Rasmussen at ProtoLife are attempting something “radically different,” says chemist Andrew Pohorille, director of the NASA Center for Computational Astrobiology.
“The McCaskill-Rasmussen project is probably the most difficult and I would not bet any money on its completion by 2016,” says Pohorille. “All other projects are aimed at constructing simple forms of life as we know it. . . . Rasmussen’s vision is to construct a ‘living’ system that is truly different from terrestrial life. He wants to test the limits of what it means to be alive, with a long-term thought of creating alternative life forms on earth or looking for them elsewhere in the universe.”
Pohorille is convinced, however, that ProtoLife’s chemical experiments are heading in the right direction. “I have come to the conclusion that some sort of evolutionary strategy is more likely to succeed,” he says. “McCaskill’s group seems to arrive at the same conclusion, trying to jumpstart natural selection using microfluidics.”
Luisi at the University of Rome is deeply skeptical of ProtoLife’s chances. “The attempt at making cells without the natural macromolecules of life—DNA and enzymes—and of utilizing only synthetic chemistry, this is the great shortcoming,” he says. “If you take biological living cells as the standard, only poor approximations will be possible.”
Packard counters that while his artificial cells “won’t be able to do anything as sophisticated as contemporary cells, the real question is whether those few simple things will be interesting and powerful.” He seems convinced they will be.
Packard and Bedau acknowledge that top-down projects will probably be the first to produce artificial life. But they assert that bottom-up projects are likely to prove more valuable in the long run, both scientifically and commercially.
First, they hope to create truly alternative life forms and generate new concepts of how life might appear elsewhere in the universe. “If you’re taking existing cells and modifying them, then you might not understand a lot of why things are working, because nature has provided it,” Bedau says. “We are not constrained by the way life arose.” The commercial advantage comes from developing capabilities beyond the limits of natural life forms. “So, for example, you could make forms of life that depend on food that is toxic to every known form of life,” he says.
And Packard has a lot riding on that possibility. The European Commission has contributed about half-a-million euros to ProtoLife’s operating budget; Packard has invested three times that, and has brought in other investors as well. So while his interest in the venture is partly intellectual, he also firmly believes that a profitable business can develop out of the research. “Even though Prediction Company was successful, it didn’t give me enough liberty that I can treat this investment lightly,” he says. “If I ever become convinced there’s no business possibility, I’ll instantly dissolve the company.”
Playing God?
The bottom-up approach also brings with it the prospect of more profound ethical challenges, not least the affront such a feat could deliver to religious beliefs based on the singular, life-giving power of a divine creator. “If you really can create life from scratch out of inorganic materials,” says Bedau, “it’ll be the last straw to that whole house Darwin knocked over. You can watch someone do it, and you can look under a microscope and there it is.”
Bedau and ProtoLife business manager Emily Parke ’04 are working on a book of essays on ethical implications and potential consequences of artificial life research. With something so unprecedented, it’s hard to imagine what the environmental consequences could be. Packard argues that building artificial cells from scratch is likely to be less risky than doing so using natural organisms that have been genetically manipulated. His reasoning is that modified DNA-based life can readily interact with other DNA-based life.
Bedau suggests that the first generation of artificial cells will be extremely feeble and utterly dependent on human intervention to survive. He expects the work to proceed incrementally, with many opportunities to halt the research and development if unexpected dangers emerge.
“All the time, we do things that change the world around us,” he says, “and it’s not necessarily bad to do that. I think it’s good to do it in a responsible and thoughtful way. Change is happening all the time anyway, and I don’t think that we should be afraid of stepping up to the plate.”
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Of course, you know, if they fail, this will only prove intelligent design, right?
Perhaps their work will be useful as an enhancement of my solar-powered-encphalotropic-homing-dart.
Of course if they succeed they can dine a Murano and if the fail at Burano. (As long as their Packard doesn't get pushed off Lido Pier.)
Besides that, whatever they do in the lab has nothing to do with what happens in the wild. After all, were they there?
Of course, you know, if they fail, this will only prove intelligent design, right?
Besides that, whatever they do in the lab has nothing to do with what happens in the wild. After all, were they there?"
And you both know they have to get the job done in under 6000 years? Right?
"Nevertheless, he and Bedau are confident that it can be done within a decade. Their competitors agree. “I do think it is possible, although many challenges remain,” says Jack Szostak of Harvard University. "
Szostak is one high powered dude. If he thinks it's possible, it's not just hopeful thinking.
"Of course, you know, if they succeed, this will only prove intelligent design, right? Of course, you know, if they fail, this will only prove intelligent design, right?"
LOL. So true. I got the same response with the article about the 100 or so year long Brit experiment to recreate the natural speciation of cauliflower, broccli, asparigus, and cabbage from wild kale.
It succeded, but took some time. The response was the selective breeding was evidence of intelligent design, instead of a re-creation of the natural speciation.
Of course, I concur that the universe was designed so intelligently He knew evolution would occur just as He wanted it. The Great Cakebaker of the Universe.
Only GOd can create life. So if they do it, well, then, uh....
(I guess they are God...)
I concur wholeheartedly. But who knows - maybe He did do the whole deal in 6 days 6000 years ago (or 10 minutes ago) and just made it look like it evolved naturally - could you disprove that?
The whole point is, these aren't scientific views; intelligent design is just fine as a spiritual philosophy, but it just doesn't play by the criteria required of science the way evolutionary theory does.
"Of course, I concur that the universe was designed so intelligently He knew evolution would occur just as He wanted it. The Great Cakebaker of the Universe."
LOL I just picture some guy making it to the gates of heaven, and upon meeting God discovers that God is actually a huge one celled organism. The guy says, “But God, you said that you created us in your image! Why did you tell us that?” God replies, “I did create you in my image. I also told you to go forth and multiply.”
Ah, the maybe He planted dinosaur bones just to screw with us theory.
Possible, I suppose. But not really His style.
Intentionally obscure text, which forces us to study His Word and pray for guidence --- yeah, His style.
Thanks for the ping!
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