by Ira Flatow
And if Guinness is not your brew, the bubbles will do their thing in other carbonated beverages too. “The bubbles are small enough to be pushed down by the liquid,” said Alexander, now a professor at the University of Edinburgh in Scotland. “We’ve shown [that] you can do this with any liquid, really—water with a fizzing tablet in it, for example.” Message to Alka-Seltzer: Take notice.
Okay, so much for winning a bet. But who cares?
Zare, an expert on carbonation, says that the bubbles of CO2 in seltzer, champagne, and beer all float to the top differently. “It’s just paying attention to the world around you and trying to figure out why things happen the way they do,” Alexander added. “In that case, anyone that goes into a pub and orders a pint of Guinness is a scientist.”
CHAPTER THIRTY-THREE
OPEN-SOURCE BIOLOGY
The power of the open-source concept isn’t so much the cost, it’s the community.
—RICHARD JEFFERSON
While to many people the computer world is divided into two camps—Mac people and PC people—there is a third camp that gets less attention: the open-source folks. These people are united to create software tools and even computer systems, such as UNIX and Linux, that are free to be used by anyone. You can download them on the Internet and run them on your computer at no charge.
That idea is now beginning to spread through the world of biology. Why not create open-source tools for biologists who can’t afford to buy the name-brand tools to help in their work in genetic engineering? To help developing countries make the products they need but can’t afford to buy?
“If we’re going to solve any of the problems that are really aching for a lot of the world, that part of the world has to solve the problems themselves,” says Dr. Richard Jefferson, chairman, chief executive officer, and chief scientist of CAMBIA, a nonprofit biotech research organization based in Canberra, Australia. Jefferson’s BIOS initiative has taken the unheard of step of taking biotechnology into the open-source community.
For example, topping the list of important techniques in genetic engineering are a set of tools, one used to insert genes into a genome and another to help figure out in which cells those inserted genes ended up. These tools help you slice and dice the genome and put in new genetic information to create a unique product. But most of those tools are controlled by a few big biotech companies. And while they might be willing to license those tools to university researchers, for instance, they’re not so open to handing those tools over for free to people actually planning to make seeds for farmers in developing countries where they can’t afford to buy new seeds each growing season.
Jefferson and CAMBIA have been able to develop alternative tools for doing some of these key genetic engineering processes, methods that they say don’t infringe on any of those patents owned by the big guys. And they’re offering to make those tools freely available, free to others to use or expand, sort of the biological equivalent of open-source software, like Linux and the others. You can use them for free. You can improve them, but you have to put them back into the public domain so other people can use them, because if you wait for others to give you the tools, you may have to wait for a long time.
“When you talked about open source being basically tools for free, the real issue is that they can be designed and built and tuned by a large community. So the power of the open-source concept isn’t so much the cost, it’s the community.”
One project Jefferson has been working on for decades involves giving the worldwide community the open-source tools and methods it needs for transferring genes into plants. It improves on the standard, patented method of using a common bacterium to carry the new genes into the plant.
“You take a soil bacterium called Agrobacterium that naturally lives with plants, which forms, under normal conditions, a pathogenic relationship. Basically it makes galls, like tumors, on plants. That’s a normal process, been going on for millions of years. It was discovered that in that process, the bacteria are capable of transferring part of its own genome into a plant and reengineering the plant, in fact, to feed it and clothe it, as it were.”
Jefferson and his colleagues wanted to make use of this talented bacteria. They wanted to genetically engineer the bacterium, to improve it. “Basically we think we could do something that works better. The downside: Agrobacterium is naturally a pathogen. That means that it causes diseases in plants.” So since the 1980s, Jefferson and others in his field have been working to “disarm” the plant so that it no longer made tumors but still could become infected.
“We decided to try to convince or coax some very benign bacteria that naturally live in a symbiotic relationship with plants and ask them, basically by minor adjustments, if they can transfer genes into plants. And the surprising and exciting observation is that yes, they can.”
But that’s when he realized that a morass of patents stood in his way of introducing this method into the open-source community. “We realized that the patents claim all aspects of methodology, the materials, the tricks, the tunings, and it became what we call a patent thicket, with literally hundreds of patents. So it’s not so much that it’s dominated by one multinational; it’s that there are so many patents involved that very often it only takes one out of this giant Tower of Babel of patents to be denied to stop the whole thing from working.”
The open-source community bypassed the problem, freeing up the tools for improving the bacteria and providing a set of open-source tools that people could use to avoid the patent mess. “It turns out that this has been a need that’s been very sorely felt by a lot of people in the science community and especially in the development community. There are countless excellent scientists totally committed in the developing world or, in fact, in small and medium enterprises in the U.S. and the UK and Europe, Australia, that are dying to get out there and start innovating on behalf of smaller markets instead of just the big-margin innovations.”
And what kind of innovations might we see, now that these tools have been unleashed? Jefferson says that “part of the beauty of open source is its lack of prescriptiveness from one guy like me or one person.” In other words, the sky’s the limit. Take what you need.
“If people have needs that are legitimate and they think that they’re not being served by existing technology, the power of open source is the ability to craft the technology depending on your needs and your view that you are not being served by existing technology.”
Making the tools freely available to private individuals does not mean that such folks aren’t free to profit from their innovative use of the tools. Jefferson says there needs to be a distinction between the “tools of innovation, which we feel are an absolute fundamental human right, and the fruits of innovation,” which can be proprietary. For example, let’s say that some young scientist makes use of these tools and she uses them to develop an improved rice strain “that she thinks has the cat’s meow properties and she wants to market it with her own trademark and her own plant breeder’s varieties.
“I don’t see that that in any way suppresses the ability of other people to develop other rice varieties. And that’s the real key. As long as it doesn’t suppress free and open both competition and innovation, we see no problem with that. We don’t even see a problem with Monsanto or Syngenta using our technologies and producing new strains of corn or soybean. The real issue is not suppressing other people from providing alternatives and not suppressing other people from developing small, medium enterprise that can be so exciting to us.”
However, what is to prevent a large company from coming in and cherry-picking the best new ideas from this “creative commons” and taking out a patent on them, in effect going against the very people who developed them?
“The basic issue is that it’s not a creative commons issue. It’s a protected commons. And that protection is built into our thinking. In other words, we are not anti-intellectual property or anti-patents. We’re very much for using them wisely
and much more discreetly. But in a sense, a patent license is the very stick that goes with the carrot of the technology that says, ‘Share nicely or you don’t get to be part of the community.’ And the patent licensing and the opportunity to sue for infringement has to always be maintained as part of our structure.”
But wait. Sure, the small-business person can sue a large company for patent infringement. But what chance does a small entrepreneur have against a team of high-priced lawyers? Once again, says Jefferson, the open-source software community has been down this road and has an interesting answer.
“Look at the open-source software community, or what started out as the free-software community. The license that guides the development of Linux is called the GPL, or GNU Public License. And you know what? The total amount of money made on Linux is in the billions and billions of dollars, and do you know how many times that license has been litigated? Zero. Because they have an extraordinarily bright counsel named Eben Moglen at Columbia University in New York who, whenever there’s threat of litigation, just picks up his briefcase, goes over and talks to these people, and gets them to understand how it’s in their best interest not to. That’s the beauty of this. It’s not about confrontation. It’s about awakening people to what’s in their own self-interest and getting communities going. And it’s worked for Linux. It’s worked for the literally tens of thousands of other software programs, including the great Apache Web server, which drives most of the World Wide Web, which was developed by our colleague, Brian Behlendorf. These are innovations that are of staggering importance to the economy, and yet, by and large, the license guiding them has not been litigated. We think that we can do the same thing. You don’t have to be confrontatory to be successful.”
The same is true for the open sharing of information. An important function of the open-source community is sharing what you know—that is, once an improvement is made, that advance is placed back into public domain, where other people can use and improve on it further. But common sense says that in the business world, knowledge is power, that sharing what you know is dangerous to your business. Not so, says Jefferson. “Yochai Benkler at Yale has written a marvelous article called ‘Sharing Nicely,’ in which he looks at the economics of innovation, and it seems to be that we actually get faster and better innovation in an industry by sharing than we do by competing.”
The end product is the capability of people to tune in to their own needs. “So instead of us talking about science done for the Third World, we should rethink [it] as science done by the Third World. Every time you see a picture of someone in Africa, India, wherever else, you see a picture of a hungry person or a poor person. But what you rarely think about is that they’re a creative person, and they are. And so the issue is we have this massive untapped source of innovation, which is normal human beings that want to solve problems. And our job is not to fix the Third World. Our job is to remove the constraints to their own creativity, and that’s a huge task. It means policy, economics, not just molecular biology.”
PART XII
THE QUEST FOR IMMORTALITY
CHAPTER THIRTY-FOUR
STEM CELLS, CLONING, AND THE QUEST FOR IMMORTALITY
From my perspective as a physician, the need for this work is now greater than ever. Stem cell research can make a difference in people’s lives, and our efforts can serve as a paradigm for how we might ultimately be able to use many new developments in biology.
—DAVID T. SCADDEN, MD, HARVARD UNIVERSITY
In the movie comedy classic Monty Python and the Holy Grail, a cart rolls through the streets of a plague-stricken medieval village, while the cart driver calls out, “Bring out yer dead! Bring out yer dead!” Bodies of plague victims are piled high on the cart. But one body keeps sitting up and announcing, “Not dead yet, y’know!” If you go to Spamalot, the Broadway musical based on the Python movie, you can buy a T-shirt on sale in the lobby that says, “I’m Not Dead Yet….”
If I were you, I’d snap one up. In the future, mortality could be just another disorder that can be cured. There are two ways that could happen. You could clone your pet or perhaps your loved one or yourself. Or you could replace yourself, organ by organ, with stem cells that grow new body parts.
CLONING TO KEEP YOUR CAT FOREVER
In late 2004, a Texas woman paid $50,000 to a California company named Genetic Savings & Clone to have her late beloved cat, Nickey, cloned. Sometime later, she brought home “Little Nickey,” a nearly identical, nine-week-old kitten that she swore was her old kitty reincarnated. It was the first time an American pet had been cloned. The very first animal to be cloned was a tadpole, in the 1970s. The first cloned mammal was Dolly, a sheep born in Scotland in 1996. Since then other animals have been successfully cloned: lab animals, including cats, mice, and rhesus monkeys; livestock, including mules, pigs, and calves; and even endangered species, such as a guar, large wild oxen from India and southeast Asia, and a mouflon, a wild sheep. Genetic Savings & Clone was forced to close up shop at the end of 2006, saying in a letter to customers it was “unable to develop the technology to the point that cloning pets is commercially viable.” There were just not enough customers willing to pay the cost of cloning Snuffy, even when the price was dropped to $32,000.
In some businesses, though, that price may be a bargain. Thoroughbred racehorses, with proven racing ability, are now being cloned with the hope that the clones will give their owners a run for the money. A champion horse, with winnings of over $380,000, was cloned by a Texas breeder for the bargain price of $150,000.
Cloning your aging dog still presents more of a challenge. In August 2005, a team of South Korean scientists unveiled Snuppy, an Afghan hound who is the world’s first cloned dog. But because female dogs ovulate only once or twice a year, and at unpredictable intervals, one Snuppy required the use of more than 1,000 embryos, plus 123 surrogate mother dogs. Only 3 became pregnant, and only 1 gave birth to a healthy puppy, Snuppy. That long string of failures means a very high price tag, until dog cloning becomes a lot more efficient.
But there are other reasons to clone besides replacing a pet or breeding a winner. The usual reason for cloning plants or animals is to mass-produce rare or desirable organisms. Cloning means making an exact copy of biological material. Farmers and vegetable gardeners know that many plants and vegetables, including grass, potatoes, and onions, clone themselves. These plants send out a kind of modified stem called a runner. Wherever the runner takes root, a new plant grows, doubling your crop.
If you have potted plants that you cultivate indoors, you’ve probably done some cloning yourself. You’re certainly familiar with taking a leaf cutting from one plant and growing a new one. If you’ve ever done that, you’ve just cloned your original plant. (I have a Christmas cactus that is now the grandchild of the original.) You can do this because the end of your cutting forms a mass of nonspecialized cells called a callus. With the right amounts of soil, light, water, and nutrients, the callus will divide and begin to form specialized root and stem cells—growing into a new plant.
Then there’s tissue culture propagation, which botanical scientists and orchid fanciers use to grow rare plants. You can take pieces of specialized roots from a plant, break those roots up into root cells, and grow them in special culture. In nutrient-rich culture, the specialized cells become unspecialized, or dedifferentiated, into calluses. With the help of plant hormones, the calluses can grow into new plants that are identical to the original plant from which you took root pieces.
Besides plants, some animals—including humans—clone naturally. Identical twins are clones. Under certain environmental conditions, the unfertilized eggs of some animals—small invertebrates, worms, some species of fish, lizards, and frogs—can develop into full-grown adults. This process is called parthenogenesis, and the offspring are clones of the females that laid the eggs.
DIFFERENT TYPES OF CLONING
Although cloning is often used as a blanket term, there are three
separate and very different types of cloning. The first is recombinant DNA technology, or DNA cloning, which is used all the time in molecular biology labs. To make more of the same DNA fragment for study, a scientist transfers it from one organism into a self-replicating genetic element, such as a bacterium, yeast, or virus. The DNA then can be replicated in a foreign host cell.
DNA cloning would be very useful in gene therapy. The 1992 movie Lorenzo’s Oil, based on a real case of a boy born with a rare genetic illness that wasn’t discovered until the 1980s, is an excellent primer on molecular biology and the promise it offers to cure inherited illnesses. Gene therapy sounds simple: You could remove defective genes from a sick person, clone healthy genes, and use a harmless virus to convey them to the patient’s cells, where they would replicate themselves and take the places of the defective genes.
Unfortunately, right now, gene therapy is far from being therapy. In 1999, 18-year-old Jesse Gelsinger, who suffered from a rare metabolic genetic disorder, died in the course of a gene-therapy experiment for which he’d volunteered. Since then, gene therapy has been going very slowly. The main problem for researchers has been finding the right gene carrier, or vector, that will convey healthy genes into a patient’s cells, and allow them to begin replicating themselves. Viruses are often suitable, but of course many viruses are harmful. In Gelsinger’s case, scientists used the rhinovirus, which causes the common cold. It’s also big enough to carry genes. Since Gelsinger died, scientists have been working to come up with a viable substitute.