Mutations in the mitochondrial DNA of cells dramatically increase with aging, Caltech study shows

PASADENA-Certain effects of aging could be caused by mutations in the DNA molecules of the energy-producing engines of cells known as mitochondria, according to new research from the California Institute of Technology and the University of Milan.

The study, published in the October 22 issue of the journal "Science", describes the results of skin-cell biopsies of about 30 individuals in a variety of age groups. The study concludes that damage to mitochondrial DNA dramatically increases around the age of 65.

"It's not a magic number, but we see a clear trend," says Giuseppe Attardi, who is Grace C. Steele Professor of Molecular Biology at Caltech and leader of the team authoring the paper.

Attardi and his colleagues focused their efforts on the small structures in cells known as mitochondria. Every cell can have tens to hundreds of these structures, which play an important metabolic role in the energy production that allows the cell to do its work.

Each of the mitochondria has about 10 to 20 molecules of DNA, which means that a single cell can have hundreds or thousands of mitochondrial DNA molecules.

But mitochondrial DNA is known to be susceptible to mutations over the course of a lifetime. These mutations can be due to oxidative damage, some enzyme malfunction, or even the cell's own efforts to repair itself. But prior to the new study, molecular biologists had difficulty in detecting aging-related mutations.

Over a period of about five years, Attardi and his colleagues developed a technique for detecting aging-related mutations in the main control region of mitochondrial DNA. This provided a very reliable method for determining the percentage of mitochondrial DNA molecules in a cell that had actually undergone mutations.

With this technique, they then studied tissue samples provided by the National Institutes of Health (NIH) and the University of Milan from skin biopsies. These biopsies came from individuals ranging from a 20-week-old fetus to a 101-year-old subject, which allowed the researchers to determine the prevalence of mutations in different age groups.

The results showed virtually no aging-related mutations for any of the subjects under the age of 65. But a dozen or so individuals above the age of 65 showed a dramatic increase in mutations. And not only did the rate of mutations sharply increase with age, but individuals also showed a sharp increase in mutations if they passed the age of 65 between biopsies.

Overall, the researchers found that up to 50 percent of the mitochondrial DNA molecules had been mutated in subjects 65 or over.

Attardi says future study will be needed to ascertain the precise effects of the mutations and the relationship to the known characteristics of aging. In addition, the researchers would like to know how the original mutation "amplifies," or is established in thousands of other molecules.

Also, the precise mechanism of the mutations is not known at this time. And finally, the study was done only on skin cells, although Attardi says the effect may possibly be seen in other cells of the human body.

In addition to Attardi, the other authors are Yuichi Michikawa, a senior research fellow in biology at Caltech; and Franca Mazzucchelli, Nereo Bresolin, and Guglielmo Scarlato, all of the University of Milan.

Writer: 
Robert Tindol
Writer: 

Largest Explosions in the Universe May Come from the Death of Massive Stars

PASADENA-Cosmic gamma-ray bursts, the brightest known explosions in the universe, may come from the fiery deaths of very massive stars in supernova explosions, a team of astronomers said today.

In a paper to appear today in the international journal Nature, the international team led by the California Institute of Technology presents evidence that the gamma-ray burst of March 26, 1998 (GRB 980326) is apparently associated with a supernova explosion.

This would then indicate that some gamma-ray bursts are associated with the formation of black holes during the fiery deaths of very massive stars. If true, this would be some of the first direct evidence for what produces gamma-ray bursts.

As a consequence, the team suggests that a burst of gamma rays are seen when one of the jets from the supernova's central black hole is pointed directly toward Earth. Gamma-ray bursts are brilliant flashes of high-energy radiation that occur at seemingly random times and from random places in the sky.

While these objects have been known since 1967, it was only recently demonstrated that these bursts originate from galaxies in the very distant universe and are by far the most brilliant bursts in the universe. This breakthrough was made possible due to the launch of the Italian-Dutch satellite BeppoSAX in 1996, which for the first time pinpointed the location of the bursts with a sufficient accuracy to enable their detailed studies with ground-based telescopes such as the W. M. Keck Telescope.

Despite the strides, scientists were still left wondering what produces these spectacular explosions. Various theories of their possible origins are still vigorously debated.

There are currently two popular models, both suggesting that the bursts originate in a formation of a black hole. In one model, two massive objects such as neutron stars or black holes (both of which may be end-products of previous supernova explosions) coalesce, forming a single massive black hole.

In the second model, such a black hole is produced in a catastrophic collapse of the core of a massive star. In this model, one then expects two sources of light: the "afterglow'' emission from the gamma-ray burst itself and light from the exploding star, a supernova. The afterglow rapidly declines whereas the supernova explosion gains in brightness over a period of a few weeks, and then gradually fades away.

The new study reports on the observations of GRB 980326 carried out at the W. M. Keck Observatory's 10-m telescope located atop Mauna Kea, Hawaii. As in many other cases, a visible light afterglow was found following the burst, which then rapidly faded away. However, the Caltech-led team discovered something never previously observed-a dramatic rebrightening of optical emission at the position of the gamma-ray burst.

Normally, the optical light of a gamma-ray burst vastly outshines its host galaxy for weeks. When the light from the gamma-ray burst fades, the apparent total brightness remains constant: all that remains is the light from the host galaxy.

Shrinivas R. Kulkarni of the Caltech team explains, "A month after GRB 980326, it looked as though the host galaxy was dominating the light." However, the next time the team observed, some eight months after the burst, the "galaxy" was gone.

"Galaxies do not just disappear, so we were astonished," Kulkarni said. "Clearly, what we were seeing is a new source of light brightening one month and then fading away. This is something quite new."

This unexpected rebrightening is now believed to be due to the underlying supernova created in the explosion of the massive star. The team had also obtained spectra of the object at different times, and that provided additional clues.

"The spectrum of the source right after the burst was blue, which is common," said S. George Djorgovski of Caltech. "But after a month it was very red, which was unexpected.

"That alone suggested that we were looking at some different phenomenon happening at the same location, but with a time delay of a few weeks."

Both the rebrightening and the spectrum changes are naturally explained by the presence of a supernova. The intensity of the apparent re-burst matches the peak brightness of a supernova seen in a distant galaxy, and its red spectrum also has the right color.

This represents the most direct evidence to date in favor of the massive supernova model. In this scenario, a black hole is quickly formed in the center of a massive star whose core is unable to support itself against gravity.

When the star explodes, powerful jets from the central black hole emerge along the original axis of rotation, and gamma rays are created by the jets. If the jets are not pointed toward Earth, then we see only a supernova and the effects of the exploding star. But gamma rays as well as the light from the supernova arrive at Earth if the jets are pointing in our direction.

Joshua S. Bloom, a graduate student at Caltech and lead author of the paper said, "This appears to be the smoking gun for the origin of some gamma-ray bursts, a perfect marriage of the two brightest events in the universe. It is wonderful to be a part of such a discovery."

Gamma-ray bursts, since their discovery some 30 years ago, have over 150 theoretical models about their possible origins, but only a handful can come close to describing the true trigger of the bursts.

"It is possible that there are other causes for gamma-ray bursts such as the coalescence of neutron stars," Bloom said. "Undoubtedly, astronomers will focus on unearthing new classes in the years to come."

Early reports of the results created some excitement in the astronomical community. Two other groups, from universities of Amsterdam and Chicago, in view of the work presented by the Caltech team, have reanalyzed the data on some other gamma-ray bursts. They appear to find good evidence for an underlying supernova in another well-studied gamma-ray burst.

"It is encouraging to have had such a resounding reception to an unexpected result," said Kulkarni. "Even some of the initial skeptics seem to be converted by these results."

Other members of the Caltech team are graduate student A. C. Eichelberger; postdoctoral scholars P. Côté, J. P. Blakeslee, and S. C. Odewahn; and Assistant Professor F. A. Harrison.

In addition to the members of the Caltech team, the other coauthors include M. Feroci of the BeppoSAX team; D. A. Frail of the National Radio Observatory; A. V. Filippenko, D. C. Leonard, A. G. Reiss, H. Spinrad, D. Stern, A. Bunker, B. Grossan, S. Perlmutter, and R. A. Knop of the University of California at Berkeley; A. Dey of the National Optical Astronomy Observatory; and I. M. Hook of the European Southern Observatory.

Writer: 
Robert Tindol
Writer: 

A heart medication is found effectivein treating skin cancer, Caltech researchers discover

PASADENA-Researchers have discovered that one type of drug used for human heart disease can inhibit the growth of skin cancer cells.

The drug, known as BQ788, is proving effective in suppressing skin cancer in mice, and drugs of this type could have potential for ovarian and prostate tumors as well. In the September 28, 1999, issue of the Proceedings of the National Academy of Sciences, California Institute of Technology biology professor Paul Patterson and researchers Ronit Lahav and Garrett Heffner report that the drug can stop melanoma tumor growth and even reduce tumors in some cases.

Further, the drug seems to be effective both as a direct treatment of the tumor and when injected systemically into the animal. The latter result is particularly promising as it has the potential for also suppressing metastasis, or the spread of tumors to other organs, says Patterson.

"If you went to the doctor with a tumor on the skin, he would take it out immediately," says Patterson, who is executive officer for the Division of Biology at Caltech. "So the first line of treatment is to surgically excise the tumor, and if it's a superficial tumor, you essentially have a complete cure.

"But the worry is when the tumor has penetrated more deeply and already metastasized," he says. "We think this drug could turn out to be an effective way to stop cancer cells from spreading, or at least stop their growth if they have already spread."

The strategy is based on the targeting of "growth factors," or proteins that cells use to stimulate their growth. The cancerous state represents a reversal of healthy, mature cells to a state similar to that of embryonic cells. In other words, cancerous cells tend to multiply rapidly, just as cells do in a developing embryo.

Lahav, the lead author on the paper, reasoned that melanoma cancer cells perhaps use a growth factor similar to that employed by their precursor cells in the embryo. She showed that such a growth factor, called endothelin, acts on the embryonic cells, and is also made by the cancer cells. By serendipity, the heart drug BQ788 is an antagonist for the endothelin receptor B. Thus, BQ788 is a substance that disrupts the receptor from performing its function in the cell.

Lahav found that this drug can stop human melanoma cell growth when introduced into cell cultures. In fact, the drug not only makes the cells stop dividing, but it can also kill such cells.

When the drug was given to mice with tumors, tumor growth slowed dramatically, and in some cases even regressed.

"It works whether you inject it into the tumor or into the body cavity," Patterson says. "In about half the mice, the tumors actually shrank."

Patterson says there is reason to think this type of drug could also work on certain other cancers (ovarian, prostate) where runaway cell growth may also be controlled by the same growth factor, endothelin.

Ronit Lahav is a postdoctoral scholar from Israel, and Garrett Heffner is a Caltech sophomore who participated in this research the summer after graduating from high school.

Writer: 
Robert Tindol
Writer: 

Gene linked to human kidney disease is also responsible for mating in roundworms

PASADENA-For a male nematode, the LOV-1 gene couldn't be more aptly named. The millimeter-long roundworm, if its LOV-1 gene is functioning properly, has the eagerness to mate and the instincts to perform successfully.

But if the LOV-1 gene is disabled, the male nematode is truly clueless. The fact that "LOV" is an acronym for "location of vulva" pretty much says it all.

While there is no such single gene controlling sexual interest and instinct in humans, California Institute of Technology researchers who recently identified the LOV-1 gene say there is a similar human gene involved in a type of kidney disease.

In the Sept. 23 issue of the British journal Nature, Caltech researchers Paul Sternberg and Maureen Barr write of their discovery that the LOV-1 gene has a sensory role in nematodes. The human homolog (or counterpart) is PKD1, or polycystic kidney disease gene 1.

In other words, a male nematode that has this particular gene intact is able and willing to mate, while a human with the gene intact is disease-free. But if the genes are respectively knocked out, the nematode is sexually dysfunctional and the human is prone to autosomal dominant polycystic kidney disease, a serious disease that afflicts about one in 1,000 people and may ultimately result in renal failure.

"This is a surprise," says Sternberg, a biology professor at Caltech. "We can only speculate on what the connection might be."

PKD1 and a second gene, PKD2, account for about 95 percent of all cases of autosomal dominant polycystic kidney disease. These genes cause the human body to produce polycystin 1 and polycystin 2, which are thought to work somehow in concert at the molecular level.

In an analogous manner, the LOV-1 gene also seems to work in concert with the PKD-2 gene, which in nematodes is the counterpart of the PKD2 gene in humans. The fact that the genes in both humans and nematodes seem to work in pairs actually strengthens the likelihood that there is some underlying molecular relationship, Sternberg says.

Much of the lab work leading to this discovery was done by Maureen Barr, a postdoctoral scholar in Sternberg's lab who painstakingly watched in a microscope for male nematodes who were not successfully mating.

Barr then singled out the dysfunctional males and used standard genetic screening techniques and DNA sequencing analysis to identify the LOV-1 gene, which when mutated, is responsible for the lack of mating behavior.

While the researchers are not clear on why a gene involved in mating behavior in one species would be involved in disease in another, they say there could be a couple of possible explanations.

For one thing, the connection between the human gene and the worm gene might be very basic. Perhaps the gene is involved in setting up polarity of human kidney cells and polarity of worm neurons that govern sexual behavior.

In the case of the worm, the LOV-1 might actually act as part of a sensory signaling pathway responding to the presence of a mating partner by altering the electrical properties of the specific nerve cell that senses the mate.

Or perhaps the underlying relationship has to do with cell structure, Sternberg says. In this case, the LOV-1 protein might function as a molecular scaffold for other molecules, or promote the assembly of many molecules to create structures such as the sensory neuronal cilia.

Sternberg and Barr say the scientific goal of the study was to investigate ways in which genes influence behavior. But the findings could also serendipitously point to new avenues for research on autosomal dominant polycystic kidney disease.

"This is a mystery disease, so it could be that renal failure is just the first defect in a disease with broader manifestations," Sternberg says. In that case, improved knowledge at the molecular level could lead to different approaches in identifying treatments or even a cure.

"Here's a new way to study the basic mechanism," Sternberg says.

Writer: 
Robert Tindol
Writer: 

Researchers mutate digital organisms

PASADENA-In a study that could point to a new way of predicting what extraterrestrial life might be like, a team of California Institute of Technology, UCLA and Michigan State researchers have shown that "digital organisms" respond to mutations in ways closely resembling the mutations of actual organisms like bacteria, fungi and fruit flies.

In the Aug. 12 issue of the journal Nature, Caltech computation and neural systems researcher Chris Adami and his colleagues explain the results they have obtained by designing computer programs to be digital organisms that can self-replicate, mutate and adapt by a process analogous to natural selection in nature.

In the study, the authors conclude that complex organisms are more robust than simple ones with respect to how significantly the organisms are affected by single and multiple mutations. Further, the study shows that the overall effect of many mutations can actually result in higher fitness of a complex organism than one would predict from multiplying together the effect of individual mutations.

This latter result tracks closely with experiments with actual simple organisms like bacteria, fungi and fruit flies in which frequent interactions among mutations are observed. But Adami says the conclusions are particularly exciting because the "artificial petri dish" approach demonstrates that digital organisms can be used by researchers to answer important biological questions.

"The advantages are that it's very simple, and that it abstracts the system as much as possible," Adami says. "It's very difficult to ask very fundamental questions about life with a living system because the living system is very complex after four billion years of evolution.

"Life on Earth is all due to one event a long time ago," he says. "Everything we see is related to one accident, so if we look back at this, can we learn something about life in general?"

The answer has implications for future searches for life elsewhere in the solar system and universe, because no one really knows exactly how life got started and how it proceeded to grow in complexity. Therefore, no one really knows all the ground rules of life.

"If we go somewhere else, are we going to find life that is similar or totally different? If it's similar but unrelated, then life is perhaps constrained narrowly. But if it's totally different, then maybe life is constrained very loosely."

Adami's program is based on some of the principles that are known about life and assumed likely to be true elsewhere: living systems replicate, they conserve information and they have dynamic properties that differ from other living systems and allow adaptations.

The digital organisms are based on these principles. By building a digital petri dish in which the programs "live," the researchers can allow the programs to live and fill up a niche, interact with each other, mutate and adapt to local conditions, die out, provide opportunities for other organisms to fill a niche-all the things that organisms on Earth really do, but over many eons.

"We can reconstruct the genetic tree, then change the origin of the tree slightly and rerun the entire tape of evolutionary history," Adami says. "If we change just one molecule way back, this can change everything, we discovered."

The question Adami hopes the new article in Nature will help settle is whether running experiments with digital organisms in a computer is really biology, as biologists understand it. There are skeptics, he says, but he nonetheless thinks the method will gain more believers as the work progresses.

Too, it doesn't hurt that a respected biologist with many years of outstanding accomplishments with actual petri dish cultures is now a collaborator.

"Richard Lenski is the world's expert at doing experimental evolution with E. coli," Adami says. "This paper is the first result of the collaboration, in which we repeated an experiment he has already done with E. coli.

"So I think this is the first time we have convinced biologists that artificial life is not just a pipe dream, but is answering some fundamental questions about biology."

In addition to Adami and Lenski, who is with the Center for Microbial Ecology at Michigan State University, the authors are Charles Ofria, who just earned his doctorate at Caltech in computation and neural systems; and Travis C. Collier of the UCLA Department of Organismic Biology, Ecology and Evolution.

Writer: 
Robert Tindol
Writer: 

Caltech joins effort to extend capabilities of major observatories

PASADENA—The California Institute of Technology will participate in a multi-institutional effort, funded by the National Science Foundation, to advance the field of adaptive optics, which promises to revolutionize astronomy.

The National Science Foundation's governing body, the National Science Board, has approved a proposal to establish a Center for Adaptive Optics at the University of California, Santa Cruz. As a partner institution, Caltech will bring together faculty from astronomy, planetary science, and physics to advance the use of existing adaptive optics technology at the 200-inch Hale Telescope at Palomar Observatory in California and the two 10-meter Keck Telescopes in Hawaii.

According to Mike Brown, assistant professor of planetary astronomy and leader of the Caltech team, "This effort will breathe new life into ground-based observing by giving us more sophisticated tools to view distant planetary systems." Depending on the size of the telescope, adaptive optics technology will make images 10 to 20 times sharper, giving scientists a much better view of space. "We plan on making Palomar the best at seeing very faint things next to very bright things, possible indicators of planetary systems. We can learn and experiment at Palomar, then utilize Keck for the really big discoveries."

Very few astronomers have any experience using adaptive optics. "We're hoping to quickly learn how to optimize the technology currently available and pass on that knowledge to other scientists. I expect this to bring about some exciting discoveries," said Brown.

Adaptive optics is a method to actively compensate for changing distortions that cause blurring of images. It is used in astronomy to correct for the blurring effect of turbulence in the earth's atmosphere. For astronomers, adaptive optics can give ground-based telescopes the same clarity of vision that space telescopes achieve by orbiting above the earth's turbulent atmosphere.

Astronomers have already started to reap the benefits of applying adaptive optics to their research. A team headed by Dr. Richard Dekany at the Jet Propulsion Laboratory recently conducted a highly successful first test of an adaptive optics system on the 200-inch Hale Telescope at Palomar Observatory. Enhanced high-resolution images of excellent quality were obtained of the ring system of Uranus and of the Lagoon Nebula.

The 27 partner institutions of the Center for Adaptive Optics will include Caltech, UC Berkeley, UC San Diego, UCLA, UC Irvine, the University of Chicago, the University of Rochester, the University of Houston, Indiana University, Lawrence Livermore National Laboratory, and 17 other national laboratory, industry, and international partners.

The center will provide the sustained effort needed to bring adaptive optics from promise to widespread use. It will conduct research, educate students, develop new instruments, and disseminate knowledge about adaptive optics to the broader scientific community.

Caltech participants will include Shri Kulkarni, Chuck Steidel, Mark Metzger, and Keith Matthews from astronomy, and Christopher Martin from physics.

Palomar Observatory is located near San Diego, Calif., and is owned and operated by Caltech. Caltech and the University of California jointly operate the W. M. Keck Observatory, which houses the world's two largest optical and infared telescopes and is located on Mauna Kea, Hawaii.

Writer: 
Sue Pitts McHugh
Writer: 

Advanced networks and ubiquitous computing to be the focus of new technology center

PASADENA-The David and Ellen Lee Family Foundation has donated $10 million to the California Institute of Technology for a center to improve computer networking through innovations such as wireless links.

The center will include broad participation from Caltech researchers in a variety of disciplines, from electrical engineering, computer science, and applied physics to economics. The center will develop research programs in advanced networking, sponsor seminars and cross-disciplinary teaching programs, develop technology exchange programs with industry, and encourage entrepreneurship in the area of advanced networking.

The new campus facility will be named the Lee Center for Advanced Networking, according to Caltech president David Baltimore.

"Our goal is to create new communication technologies that will help change the world," Baltimore says. "The generosity and vision of David and Ellen Lee have made it possible for Caltech to become a leader in advanced computer networking."

Caltech provost Steve Koonin says the new center will help revolutionize the ways in which information moves from place to place. "With this donation, we will develop information space where people can communicate, regardless of where they are geographically, or whether they are mobile or stationary."

The center will focus on creating a worldwide distributed computing system that connects people and appliances through wireless and high-bandwidth wired channels, Koonin says.

Dr. David L. Lee is president and chief operating officer at Global Crossing and holds a doctorate from Caltech in physics with a minor in economics.

"Deregulation in the telecommunications industry and breakthroughs in optronics technologies have caused fundamental, structural changes in global communications," said Lee. "New types of global networks are being built at a fraction of the cost of the legacy networks they replace. A world of seamless, ubiquitous connectivity is now within our reach, with a networked computer in almost every human tool and habitat. It is my hope that this new center will help realize that new future."

"The traditionally interdisciplinary nature of Caltech will help develop unique research and teaching programs that span all the components of engineering, sciences, and the social sciences," says Caltech Professor of Engineering David Rutledge, who will be charter director of the center. "The research will span everything from optical fiber and silicon substrates, to applications such as e-commerce, e-service, and distance learning."

E-service, for example, would expand communications far beyond the capabilities of standard e-mail. An automobile might be installed with wireless communication so that an automated message is sent to emergency services when the car's air bag goes off in an accident.

Virtual learning and long-distance collaboration, too, would greatly benefit from improved networking capabilities. In an age when social and market forces are making the boundaries between workplace and home more vague, the new technologies could allow parents to do their jobs while at home with much greater ease than currently possible. Multinational collaborations would be easier, and state-of-the-art teaching at remote facilities would be improved.

Caltech faculty to initially be associated with the center:

-David Rutledge, director, Lee Center for Advanced Networking; and executive officer for electrical engineering;

- Jehoshua Bruck, professor of computation and neural systems and electrical engineering;

-Mani Chandy, Simon Ramo Professor of Computer Science and executive officer for computer science;

-John Doyle, professor of control and dynamical systems and electrical engineering;

-Michelle Effros, assistant professor of electrical engineering;

-Ali Hajimiri, assistant professor of electrical engineering;

-Robert McEliece, Allen E. Puckett Professor and professor of electrical engineering;

-Charles Plott, Edwin S. Harkness Professor of Economics and Political Science and director of the Caltech Laboratory for Experimental Economics and Political Science;

-Kerry Vahala, professor of applied physics.

With the support of the grant announced today, Caltech will also recruit new faculty members to expand the scope and depth of the Center's research capabilities.

 

Writer: 
Robert Tindol
Writer: 

Many life-bearing planets could exist in interstellar space, according to Caltech planetary science professor

PASADENA-Long ago in a solar system not at all far away, there could have existed about five to 10 Earth-like planets in Jupiter-crossing orbits.

These planets today could harbor life somewhere in interstellar space, according to a planetary scientist at the California Institute of Technology.

In the July 1 issue of the journal Nature, Caltech professor Dave Stevenson says in a new study that such objects could be life-sustaining due especially to the molecular hydrogen they accreted when the solar system formed long ago.

Called "interstellar planets" because they would exist between the stars but no longer in orbit around an original parent star, they have never been directly observed or proved to even exist. But based on what scientists know about the way matter should fall together in forming a solar system, such Earth-like planets could definitely have been formed.

Over a period of several million years, one of two things happened to these planets: either they slammed into Jupiter and made it even bigger, or else they came so close to Jupiter that they were catapulted by gravity completely out of the solar system, never to return.

Because these bodies formed when the solar system was permeated with hydrogen gas, they retained a dense atmosphere of hydrogen, allowing them to have surfaces with temperatures not too different from Earth, and possibly water oceans.

Stevenson writes that in the absence of sunlight, the natural radioactivity inside an Earth-like planet would only be sufficient to raise the radiating temperature of the body to 30 degrees above absolute zero (that's about minus 400 Fahrenheit). But the expected dense hydrogen atmosphere would prevent the surface from radiating effectively-just like the greenhouse effect on Earth, but more so.

As a result, the surface could have a similar temperature to the current Earth surface, allowing water oceans and a surface pressure similar to that at the bottom of Earth's oceans. For this to happen, the interstellar planet would probably need to be at least half Earth's mass.

Therefore, the energy source would be much the same as that which drives geothermal energy and plate tectonics on Earth.

It is not known whether geothermal heat alone is sufficent to allow life to originate, and the amount of energy is small compared to sunlight, suggesting that the amount of biological activity would also be small. But the existence of life in such an environment would be of great interest even if the mass of living matter were small.

The heat energy, and especially variations in temperature, could potentially allow life to get going, Stevenson says.

"I'm not saying that these objects have life, but everyone agrees that life requires disequilibrium," he says. "So there has to be a way to get free energy, because that's what drives biochemical processes.

"These objects could have weather, variations in clouds, oceans...even lightning."

If life exists on such objects, an open question is how complex it could be, Stevenson says. "I don't think anyone knows what is required to drive biological evolution from simple to very complex systems."

These interstellar wanderers could also have arisen as a natural outcome of the formation of stars, and not just during the formation of the system we live in. In either case, such planets cannot be seen with present technology because they are so dark and cold-at least from Earth's vantage point.

Although these bodies may have warm surfaces, they would appear to us as very weak emitters of long-wavelength infrared radiation, much below current detection limits.

The best bet for even demonstrating that interstellar planets exist is to have some programmed search for occultations, he says. In other words, the object might pass occasionally in the direct line of sight between Earth and a star, and if instruments were watching, the light of the star might dim or even flicker out for a time.

Programs like this are already advocated for the purpose of looking for planets in orbit around other stars. But looking for interstellar planets would be even harder.

"All I'm saying is that, among the places you might want to consider for sustainable life, you might eventually want to look at these objects. They could be the most common location for life in the universe."

Writer: 
Robert Tindol

Caltech researchers use the "unnatural selection" of directed evolution to alter a bacterial enzyme

In a novel process that makes the evolution of species look like an engineering design contest, California Institute of Technology scientists have forced a bacterial strain to "evolve" a beta caratenoid enzyme . The evolved enzyme can carry out reactions that normally require other proteins and expensive agents. These reactions are important for making drugs and chemicals.

The enzyme, called a cytochrome P450, is one of a class of enzymes that inserts oxygen atoms into a huge number of compounds, according to Caltech chemical engineering and biochemistry professor Frances Arnold. In an article appearing in the June 17 issue of the journal Nature, Arnold and her team demonstrate an evolutionary process to alter the enzyme and overcome several of the natural limitations that make it inefficient and expensive to use. "The P450s do some great chemistry, but they are complex and ill-behaved," says Arnold, who helped pioneer directed evolution some years ago. "We hope to create stable P450s that need no expensive external cofactors to work. We'd like to pare them down to the absolute minimum and see how well they can do. They may well be much better catalysts without all the fancy machinery."

Nature helps these enzymes along by providing a retinue of protein assistants and complex chemicals that are either impossible or very expensive to reproduce outside a cell. In the Nature paper, the Arnold team reports the laboratory evolution of a P450 that no longer needs any of this help to catalyze its reaction.

Directed evolution has been heralded recently as a means of creating new enzymes and even whole organisms with new or vastly improved characteristics. In contrast to natural evolution, in which the survival of the fittest dictates the direction of change, directed evolution engineers enzymes for specific purposes. These purposes may have nothing to do with what the enzymes do in their natural organisms. For example, the enzymes may be better suited for removing laundry stains, or they may be used to treat diseases.

In directed evolution, the scientists dictate which enzyme characteristics will be selected in each generation, very much the way plant breeders use mutation and selective breeding to create new corn varieties or animal breeders have introduced new varieties of cattle or sheep.

In the case of the P450 enzymes, Arnold and her team wanted an enzyme that would work without any additional help. To do this, they made use of a known feature of the P450s—that hydrogen peroxide could support the reaction in the absence of the helper proteins and cofactor. Their goal was to evolve what Arnold calls this "biochemical oddity" to make it the primary pathway for the enzyme to work.

Arnold is interested in creating enzyme catalysts that could be used to manufacture drugs and chemicals. "The ideal is a rock-stable, very fast, very active enzyme that you could put in a bottle," she says. "Over the next five to 10 years, we're aiming at enzymes that the chemical industry could use." These improved enzymes could also perhaps lead eventually to new technologies that remove toxic wastes in soil or water.

"In this paper, we present the results of two generations, which makes the enzyme 20 times better than it originally was," she says. "We don't know how far we'll be able to go. But we hope that 10 more generations could result in something remarkably good. With other enzymes, for example, we have seen improvements of 500-fold over 10 generations."

Arnold's procedure for directed evolution is to first target an interesting enzyme. In the case of the current paper, the enzyme is from Pseudomonas putida, a bacterial strain that uses the P450 enzyme as a sort of "digestive aide" to eat camphor that is found in soil. The researchers then take the gene that codes for the enzyme and create millions of mutants, which they put back into a bacterial "workhorse" that generates the mutant enzymes. The scientists then screen these mutants for the desired qualities.

The best candidates from that generation can either be "bred" together to obtain further improvements, or the process can be started over again with new mutations.

Arnold says that each generation of the P450 enzyme takes about a week or two. Practically, a total effort in directed generation takes at least several months.

The other authors of the paper are Hyun Joo and Zhanglin Lin, both postdoctoral scholars in chemical engineering at Caltech.

Writer: 
Robert Tindol
Writer: 
Exclude from News Hub: 
No

Lack of Energy Makes Life on Europa Unlikely, Caltech Study Concludes

Embargoed for Release at 3 p.m. Thursday, June 3, 1999

PASADENA—Future space travelers to the watery Jovian moon Europa should probably leave their fishing tackle at home. A new study conducted by California Institute of Technology and Jet Propulsion Laboratory scientists shows that the Europan ocean is unlikely to harbor any life form more complex than single-celled organisms—and maybe not even that.

In this week's issue of the journal Science, Caltech geobiologist Eric Gaidos and coauthors Kenneth Nealson and Joseph Kirschvink show that nearly all forms of energy used by life on the Earth are unavailable to the organisms that might live beneath Europa's surface ice layer.

According to Gaidos, "One must be careful when doing comparative planetology. It is not a safe assumption to use Earth as an analogy. A liquid-water ocean on Europa does not necessarily mean there is life there."

On Earth, chemical energy is derived either from sunlight by means of photosynthesis or from the oxygen that is a byproduct. This oxygen reaches even the exotic animals inhabiting the super-hot volcanic vents in the deep sea that were discovered 20 years ago.

Even for the organisms living under ice sheets on Earth, the system is not closed. Energy from outside is available for the organisms underneath.

Unlike Earth, Europa is a closed system. The ice layer cannot be penetrated by sunlight and the only available energy in the system comes from within. This study shows that the energy available is very small compared to levels used by organisms on the Earth. It seems very unlikely that multicellular life could survive, and the lack of energy puts constraints on the likelihood of finding even hardy single-celled organisms.

Gaidos uses the analogy of an energy waterfall. "Chemical energy is falling from a high state to a low state just as water falls due to gravity. Life acts as a waterwheel in this process and harnesses the energy. However, without a source of chemical energy, the waterwheel stops."

Kirschvink adds, "Earth has a lot of metabolic energy available for life, but if you shut off the source, you shut off the system."

The study doesn't completely rule out the possibility of life, however. Gaidos says the study "assumes that the life we look for is based on the same energy sources used by life on Earth.

"The study puts limits on what life is possible," says Gaidos. "Complex life is very unlikely, but there are other possible alternatives for simple organisms to acquire the necessary energy."

One such possibility is that the organisms derive the necessary biochemical energy from oxidized iron (rust) that may exist under the ice. Other possibilities may exist, so long as there is a source of energy and life can insert its waterwheel at some point in the system.

"But we are talking about very simple organisms that can live on these energy sources. These are not multicellular creatures," Gaidos says.

Only the future will reveal what scientists might find under the ice of Europa. But we do know that no fish will be biting.

Writer: 
Robert Tindol
Writer: 

Pages

Subscribe to RSS - research_news