Are Chimeras People Too?

As Britain prepares to debate a provision in Parliament to allow the creation of chimeric hybrids of humans and animals (see blog of May 24, 2007), the Catholic bishops of England and Wales have told a joint committee in the British legislature that these chimeras should be allowed to go to term and be born.

What these Catholic prelates object to is the proposed destruction of chimeric embryos after 14 days. They believe that embryos that are partially human should be implanted in human mothers, and that they should be afforded all the rights of a 100 percent human. According to a recent article in London's Telegraph,

The bishops, who believe that life begins at conception, said that they opposed the creation of any embryo solely for research, but they were also anxious to limit the destruction of such life once it had been brought into existence.

In their submission to the committee, they said: "At the very least, embryos with a preponderance of human genes should be assumed to be embryonic human beings, and should be treated accordingly.

"In particular, it should not be a crime to transfer them, or other human embryos, to the body of the woman providing the ovum, in cases where a human ovum has been used to create them.

"Such a woman is the genetic mother, or partial mother, of the embryo; should she have a change of heart and wish to carry her child to term, she should not be prevented from doing so."

In the fifteenth and sixteenth centuries, astronomers sanctioned by the Catholic Church, such as Christopher Clavius, labored to create a scientific cosmological framework that conformed to both church dogma and the latest observations and data coming from astronomers, such as Nicolas Copernicus, that contradicted the dogma that the earth was at the center of the universe. Attempts to reconcile the two positions led to convoluted and bizarre justifications that were eventually abandoned by nearly everyone.

Arguing that hybrid species with human components deserve to be born requires similar leaps of logic. For instance, if one truly believes that a partially human embryo is a full human, then what about all the animals that share a preponderance of DNA with us humans already, such as other primates, dogs, and mice? What percentage of "human" DNA, which is not exclusively human anyway, makes an organism truly "human"?

Figuring out what is human and what is not is an intriguing question as scientists begin to create human-hybrid embryos, but that's a separate issue from what the bishops are discussing. What they really oppose is human embryos being used for research or treatment, and then destroyed. For now, almost no one wants these bundles of inter-species DNA to go to term. That's not the point. The idea is to develop therapies using hybrid embryos to treat and cure disease. Creating a dog-person is not on anyone's agenda.

Extreme Metagenomics: Chasing Bugs in the Bowels of the Earth

As microbiologists scour the earth's most inaccessible places to find ever more weird--and potentially useful--microbugs, I'm half-expecting a new reality show to pop up on the Sci-Fi Channel, or perhaps ESPN-5: Extreme Microbes!

Scientists studying the tiniest of bugs have long traveled to peculiar locales, but now the entire field has been invigorated afresh by the new age of metagenomics--the study of groupings of bacteria found in, say, a bucket of water, a patch of human skin, or a spade full of muck. Armed with sophisticated new technologies to identify millions of different kinds of bacteria inhabiting a specific mini environment, the new "metageneticists" are deploying to nooks and crannies ranging from acid spills to deep caverns in search of microbial communities.

In News@Nature.com, writer Josie Glausiusz describes a spelunking expedition led by microbiologist Diana Northup a thousand feet below the earth, deep into New Mexico's Lechuguilla Cave. She and her team from the University of New Mexico hiked through tangled miles of passageways while rappelling down pits, traversing perilous edges of cliffs, and tramping around underground lakes on their way to collect bacteria that deposit manganese crusts and oxidized iron on cavern walls. Northup is also part of a multiple-university consortium appropriately dubbed SLIME--Subsurface Life in Mineral Environments.

A previous attempt by Northup to snatch up a batch of manganese- and iron-dropping critters failed to produce results because she and her team inadvertently contaminated their samples with fungi that they had brought in on their hiking boots. Back in the lab, the fungi had popped up like weeds in the agar plates when Northup tried to grow the bacteria. This time the team brought clean suits--a misnomer for a posse of microbe hunters who were exceptionally filthy with sweat and muck after their subterranean trek.

Northup also decided to take no chances in growing her samples, so she brought in glass tubes to get her bugs started in their own environment of absolute darkness, cool temperatures, and high humidity. Scientists have found that the classic method for growing bacteria--adding samples to agar-rich petri dishes--doesn't work for an estimated 99.9 percent of microbes, which thrive best in their own ecological soup. This is one reason that metagenomics is taking off. Another is that advances in technology now allow researchers to sequence all DNA in a meta sample to find out how many species and gene variants appear in a given eco niche.

Perhaps the best known metagenomicist is J. Craig Venter, whose Sorcerer II Global Ocean Sampling Expedition announced in March that it had discovered six million new genes and thousands of new protein families, some of which may offer novel solutions for storing and producing energy, among other possibilities. Others are finding microbes that might clean up pollution or produce newfangled antibiotics.

Writer Glausiusz describes the search for antibiotics in her article, as well as a nascent move to commercialize discoveries resulting from the search for slime:

Meanwhile, Kim Lewis and Slava Epstein of Northeastern University in Boston, Massachusetts, are trolling the depths of the uncultured for new antibiotics using a diffusion chamber in which microbes are suffused in the conditions of their natural environment--soil, for example, or sea water plus marine sediments. Lewis and Epstein have founded the company NovoBiotic to capitalize on their cultures. "The practical benefits are enormous," Lewis says. "If you want to discover new stuff, you want to go to organisms you haven't seen before. It's reasonable to assume that 99% of the remaining bacteria will have at least some useful antibiotics."

The spelunking Northup has begun to find antibiotics in her samples. Initially, though, she strove to grow crust-forming cave bacteria to understand their basic biology. "One of the reasons we culture rather than do DNA sequences is because we want to catch them in the act of precipitating the minerals, so that we can say definitely, 'These guys can do it,'" she says.

I encourage you to read the entire article on News@Nature.com; it's creepy-crawly stuff and utterly fascinating. I also suggest that you attend Technology Review's Emerging Technologies Conference at MIT from September 25 through 27, where I will be moderating a panel on metagenomics.

Glausiusz, Josie, "Extreme culture: From acid mine drainage to the bowels of the Earth," Josie Glausiusz reports how researchers are taking great pains to grow recalcitrant bacteria, Nature, Published online: 20 June 2007; | doi:10.1038/447905a

Did Primordial Chefs Feed Our Giant Brains?

Around 1.9 million years ago, something extraordinary happened to the chimp-like hominids called Homo erectus. Their brains began to enlarge, becoming double the size of those of chimpanzees. Several theories are beginning to coalesce about why this happened. One is that early people began to eat more and better meat around this time, which allowed more calories to be consumed faster. This led to a shrinking of gastrointestinal organs and an increase in brain size that essentially traded guts for gray matter.

Our big brains need this extra energy. Modern humans eat about the same number of calories as other primates that approximate their weight, but we suck up an average of 25 percent of our body's energy expenditure, compared with the 8 percent sucked up by apes. Human babies use 60 percent of their energy to feed their heads.

Anthropologists have assumed that H. erectus ate their burgers and steaks raw, since most early fire pits discovered so far date back about 500,000 years, with the oldest, in Israel, dating back 790,000 years. Charred stones and tools associated with human sites have been discovered that date back as much as 1.5 million years, but these might have been naturally occurring fires.

Now Harvard University's Richard Wrangham has provided some evidence that the very distant ancestors of America's top chefs indeed may have learned to cook their antelope and rabbit. Cooking makes both plants and meat softer and easier to chew, providing more calories with less effort. What's more, human teeth got smaller and duller at around this time, which is the opposite of what would have happened if people had had to rip and chew lots of raw meat.

Wrangham worked with Stephen Secor, an animal physiologist from the University of Alabama at Tuscaloosa, who ran experiments to test the energy required by pythons to consume cooked versus raw meat; Secor also ran experiments on mice to gauge the impact of cooked versus raw meat. The snakes used almost 25 percent less energy chowing down cooked meat; the mice gained more weight and grew slightly longer. The fast turnaround in the mice indicates that cooked meat might have had a quick and dramatic evolutionary impact on early people.

Reducing the time and energy required to chew and digest raw meat means more energy available for other uses--such as feeding a voracious brain that's getting bigger and bigger. Wrangham also thinks that the modern rise in the consumption of cooked meat may contribute to the obesity epidemic; the same goes for processed food, which is even easier to eat and digest. Wrangham presented his findings at a recent paleoanthropology meeting in Cambridge, in the United Kingdom.

Paleoanthropologists are excited by Wrangham's findings and provocative ideas, but the absence of definitive proof of campfires appearing at the same time that human brains doubled in size is a problem. Many still believe that humanity's first cooked meal came much later--about 800,000 to 500,000 years ago, when the human noggin began growing again, expanding by about 30 percent into the modern-size brain.

One question that I'd like to ask evolutionary biologists and paleoanthropologists is why the huge expansion of our brains led to such seemingly unique traits in humans like advanced language skills and acute self-awareness. Would these same traits develop in other mammals if they were fed a diet of broiled beef over several generations? I wonder how many generations of mice it would take to replicate what happened to us--that is, I'd like to see if mouse brains double or triple in size, and also what our furry little friends would do with all that extra neural material.

Citation:

Science 15 June 2007:Vol. 316. no. 5831, pp. 1558 - 1560 DOI: 10.1126/science.316.5831.1558

Craig Venter: The Bill Gates of Artificial Life?

There he goes again, says a group of scientists and activists alarmed by the latest rebel moves of J. Craig Venter.

Since butting heads with the scientific establishment during the sequencing of the human genome--and coming out rich and famous in the process--Venter has had the moxie and smarts to know just when it's time to blend science with commerce.

This time he's trying to cash in with a patent for artificial life--specifically, a designer microbe that Venter and his pals at the Venter Institute have been trying to assemble from scratch. In 1999, Venter and Nobel laureate Hamilton Smith used a simple bacterium called Mycoplasma genitalium to roughly figure out the minimal number of genes it would take for an organism to live. Since then they have been trying to synthesize this "minimal genome" inside a cell that could be augmented by additional genes to do things like produce hydrogen or gobble up carbon dioxide.

Three years ago, when I last visited Venter's institute, located in Rockville, Maryland, he told me he and his colleagues were making great progress on finishing this artificial bug. But so far there has been no announcement of success. "This is not easy to do, to build a living organism from scratch," he said at the time.

Whatever success or failure the team has had, Venter the businessman quietly filed an application last October that seeks to own the critter his lab wants to create. The U.S. Patent Office published the application (#20070122826) on May 31.

Six days later, I got an e-mail from the ETC Group, based in Ottawa, Canada, decrying the application as an attempt to launch a novel new technology onto society without knowing its full impact. ETC researcher Jim Thomas wrote this to me (and probably hundreds of other science writers):

We believe these monopoly claims signal the start of a high-stakes commercial race to synthesize and privatize synthetic life forms. And Venter's company is positioning itself to become the "Microbesoft" of synthetic biology. Before these claims go forward, society must consider their far-reaching social, ethical and environmental impacts, and have an informed debate about whether they are socially acceptable or desirable.

ETC, a group of scientists, environmentalists, and other activists, describes itself as a "civil society organization that tracks new biotechnologies and nanotechnologies." In May the group was joined by 38 organizations that called for the patent office to reject the application on several grounds. These included safety: the group raised an old fear about bioengineered organisms escaping into the environment to wreak havoc. This scenario for M. genitalium is unlikely, however, since this bacterium can only exist in a very specific environment. Other organisms made under the patent might prove more dangerous.

ETC also claims that Venter's patent should be rejected until there is a thorough discussion about whether or not anyone should own what the application calls a "free living organism that can grow and replicate." Of course, bioengineered organisms have been patented by biotech companies for years, since a landmark Supreme Court decision in 1980--but should this cover organisms made entirely from scratch? And would Venter's recipe apply to more-complex organisms, such as animals and even humans?

In its press release, ETC says,

According to synthetic biologist Drew Endy of Massachusetts Institute of Technology (MIT): "There is no technical barrier to synthesizing plants and animals, it will happen as soon as anyone pays for it." Indeed, in a recent interview (November 2006) Endy predicted that it should be possible to synthesize an entire human genome within a decade.

Well ... we'll see. Perhaps the most serious issue is publishing details of building microbes that terrorists might use to design deadly pathogens.

None of this will matter if Venter can't actually make his artificial bug. Without a functioning organism, the patent will not be issued. But assuming he will make it, or perhaps already has, ETC does have a point that I have often emphasized: society should debate and discuss radical new technologies like this before allowing entrepreneur-scientists to plunge in.

This sort of discussion occurred in the 1970s when recombinant DNA scared the willies out of some scientists and activists who feared that organisms bioengineered to make drugs might escape into the environment. Mainstream scientists reacted by holding a famous meeting at the Asilomar Conference Center in Northern California, which led to a slowdown in research to explore safety issues and to make sure the new technology would do no harm.

This process for synthetic biology has already begun. Earlier this year, a meeting of synthetic biologists at the University of California, Berkeley, issued a statement that endorses safety measures and a wide public discourse, although critics say it did not go far enough.

The question is, will the man that Time magazine once called the "bad boy of science" heed these calls for caution? He has said that he will be careful. But one thing's for sure: Craig Venter does what he likes, sometimes with flashes of brilliance, sometimes with all the grace and care of the proverbial bull in the china shop.

June 18, 2007: Addendum to Readers

After publishing this blog, a spokesperson for the Venter Institute e-mailed me to say that Craig Venter speaks often about the societal implications of synthetic biology. In 1998, the Institute of Genomic Research, founded by Venter, issued an ethical report on the topic authored by a team led by bioethicist Arthur Caplan of the University of Pennsylvania. In 2005, the policy group at the Venter Institute, along with MIT and the Center for Strategic and International Studies, were given a grant from the Sloan Foundation to review societal issues and laboratory practices surrounding synthetic genomics. (Check out the press release issued in 2005.) Their final report from this review will be issued in July.

Venter seems determined to forge ahead with his work and with his patent--which is his prerogative as a scientist. It is also the prerogative of critics to continue to challenge Venter and others as they push science to the edge of what society may or may not tolerate at the moment. In between is the great mass of society that will undoubtedly pay scant attention to either side, although the outcome of this discussion may have far-reaching implications--if Venter is able to create a truly synthetic organism.

I plan to closely follow this issue and read the Sloan-funded report next month. Let's pick up this discussion again then.

The World Trade Center: The Dust of Tragedy Lingers

Nearly five years ago, thousands of people rushed in to the site of the terrorist attack against the World Trade Center in New York City. As thousands of survivors and locals fled the burning and collapsing towers, a heroic effort was already under way to, first, save as many people as possible, then scour the ruins for survivors and bodies, and finally clean up the horrific mess.

Throughout most of this, the ruins smoldered, creating a long-term impact of this attack that few predicted at the time.

On September 14, 2001, I arrived in New York and breathed in lungfuls of the acrid stew of chemicals and ash. It made my nose tingle, and when I walked downtown to the disaster site, my eyes burned slightly, and I wished I had something to put over my mouth.

I was in Lower Manhattan for only a couple of days. Many workers labored there for weeks and months. Many of them have since come down with respiratory problems and other ailments possibly associated with a project that emphasized quick response and cleanup more than it did safety.

Now a Perspective column in the New England Journal of Medicine (NEJM) sums up some of the findings of the past five years about the dust and its aftermath. It cites studies that have measured the content of the air in the days and weeks following the attack, as well as studies that assess the health impact.

The composition of the air was mostly "coarse particles and pulverized glass fibers, asbestos, lead, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polychlorinated furans and dioxins," a toxic stew reported in great detail in a 2004 study in Environmental Health Perspectives. The dust was highly alkaline--pH 9/11.

Some of the materials were known or suspected carcinogens; others were nanoparticles of toxins that lodged in blood and cells. Most damaging were particles large and small that damaged airways and lungs. For instance, in one study, a group of firemen have 10 times the level of reduced lung function than would normally occur with age. Thousands of New Yorkers, from schoolchildren to police officers, have a persistent hacking known as the "World Trade Center cough."

According to the NEJM article, many questions linger about this long-term collateral damage inflicted by the terrorists.

Still, there are some things we will never know for certain;indeed, we do not even know with any certainty the size of theexposed population. Continued tracking of the responders shouldprovide a clearer picture of the natural history of World TradeCenter cough syndrome and should guide selection of the mosteffective therapies. The registry will be informative regardingbroad questions of health, but although it includes more than71,000 registrants, analyses of follow-up data will not revealthe existence of relatively infrequent consequences unless theadditional risks are very high. The long-term risks of cancerwill be difficult to measure with any precision, although quantitativerisk-assessment approaches should prove useful for estimatingthe maximum potential burden of cancer. But even the full suiteof research efforts in progress may never provide the evidenceneeded to answer all the questions that will be raised aboutthe long-term health effects of the events of September 11.

Curiously, no one seems to have run genetic tests to gauge the susceptibility of victims to cancer and other maladies when exposed to environmental toxins. This science, called toxicogenomics (see my May 7 blog), is in its infancy, but it may already provide some clues into who will have the worst long-term effects. Someday, testing for genes that make one more or less susceptible to environmental toxins might help in the selection of who responds to disasters that involve ash and chemicals raining down.

Of course, genetic screening for job suitability is both a positive and a negative, since the same testing process could also be used to discriminate. But in the case of disasters such as the World Trade Center and Katrina, this might be a good use of this new science.

Articles cited:

Samet, Jonathan M., et. al., "The Legacy of World Trade Center Dust", New England Journal of Medicine, Volume 356:2233-2236, May 31, 2007, Number 22

Landrigan, PJ, et. al., "Health and environmental consequences of the world trade center disaster", Environmental Health Perspectives, 2004 May;112(6):731-9

"Natural" Pot Helps Fetal Brains Connect

Whoa, dude: what's this about?

It's not, like, about smoking dope: it's about researchers in Sweden and Indiana experimenting with fetal mice whose brains naturally produce a chemical similar to Tetrahydrocannabinol (THC), the active ingredient in marijuana.

Scientists have known from studying women who smoke marijuana during pregnancy that when you add cannabinoids to fetal brain cells, it prevents neurons from making strong connections. But why?

The researchers found that the naturally occurring endocannabinoids (made by the brain) help position the rootlike feelers, called axons, that neurons use to communicate with one another. The process is highly sensitive to the amounts of the chemical, when it's released, and its location in the brain. Adding THC-like chemicals from the outside throws off this delicate balance.

When researchers added synthetic cannabinoids to the wee little mouse brains, their axons withdrew from the areas of high concentration and moved in other directions.

According to an article posted on ScientificAmerican.com,

The researchers found two groups of brain cells in embryonic mice that carried the CBR proteins for several days during late development. (Mice gestate in 18 or 19 days.) The cells were located in the cortex, the brain region that controls attention and planning in humans and other mammals.

THC would likely affect very similar brain systems in human fetuses, says neuroscientist Yasmin Hurd of the Mount Sinai School of Medicine in New York City, but its concentration would be much higher than that of any endocannabinoid. "It would have an even more pronounced effect on axonal growth and guidance," she says.

Apparently, a woman's marijuana smoking during pregnancy causes children to learn more slowly than other kids, but they are just as intelligent--and now we know why. This should convince anyone contemplating smoking a bong near a pregnant woman to cease and desist. It also adds new meaning to the term "dazed and confused."