Saving the Banana

In 2003, I met Geoffrey Arinaitwe, a Ugandan plant geneticist training at Belgium's Catholic University of Leuven--one of the early research centers developing genetically modified (GM) crops. Regardless of what you think about GM food, Arinaitwe had a compelling story: without genetic modification, the main food source of his country and many others in the tropics would die off, impacting the diet of 10 million Ugandans and hundreds of millions more poor people from Brazil to Indonesia.

Now Arinaitwe is back in Kampala, where he is poised to test the first modified bananas to be planted in Ugandan soil. A researcher at Kawanda Agricultural Research Institute,, this shy scientist with a gentle voice and slight build is waiting for GM plants to arrive from Leuven; they are expected within the month.

In 2003, I wrote a story for Seed magazine about the plight of the edible banana. Since it's seedless and therefore sterile, all bananas come from mutant plants discovered some 8,000 years ago, probably in Papua New Guinea. They have been grafted, or cloned, ever since, and developed into dozens of varieties, colors, and sizes. Bananas are ideal for the developing world because they are compact, easy to grow and transport, and highly nutritious. In these parts of the world, they are eaten raw and cooked and used to make beverages. In Uganda, they are so important that the word for banana, matooke, also means "food."

Unfortunately, with an 8,000-year-old genome, the edible banana hasn't evolved to keep up with new pests. These include the black sigatoka, a leaf-destroying fungus, which has devastated vast acres of bananas. It cripples plants and reduces output by 50 percent. Close to half the banana crop in Uganda has been afflicted as this fungus spreads around the world.

Scientists at Leuven have been working to combat the problem. Led by Rony Swennen, a team discovered that inserting a gene from rice provides significant protection for the banana with apparently no danger to either humans or the environment. Because the banana is sterile, it can't get loose in the environment, nor is there a seed allowing Monsanto or other corporations to sell it. In fact, Swennen and banana organizations around the world are prepared to provide the initial plants to farmers at a cost. Once a farmer has the plant, he or she can graft more.

Another advantage, according to Swennen and Arinaitwe, is that the GM banana greatly reduces the need to use pesticides that fend off the black sigatoka in export crops going to markets in the West. Most Ugandan farmers growing bananas for local consumption can't afford expensive pesticides, but on huge plantations in Africa and Latin America, growers use some of the highest levels of chemicals sprayed in the world to fend off fungi and other pests. This has led to reports of higher than normal instances of leukemia and sterility in growers.

By the way, organic bananas sold in the West are grown without pesticides. They are raised either in areas unaffected by the black sigatoka or are harvested out of the reduced yields of afflicted plants, further reducing the amount of fruit available to locals.

None of this convinces opponents of GM foods, who responded to my Seed article with astonishing vitriol and even some personal attacks. I'll leave it to readers to decide if inserting a rice gene into a cloned banana is repugnant and undesirable.

Almost certainly, though, critics are correct that acceptance of the modified banana may make other forms of GM foods more palatable, so to speak, particularly in much of Africa, which has largely opposed GM crops. As modified corn, cotton, and other crops become more prevalent in the West and elsewhere, it's obvious that GM creep has already begun.

As for safety, the scientists at Leuven say that their GM bananas are harmless. Now Arinaitwe will test them in Uganda to see if he and the Ugandan government agree. Hurdles remain before a rice-banana hybrid is approved and accepted. Protests are also expected, although in the end the withering, decimated crops that cover hill after hill in this country, which has an entire culture built on the banana, may make this banana update stick. We'll see.

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.

Men, Are You Tired of Being Bald?

Call before midnight tonight and have a full head of hair, guaranteed!

Okay, there is no number to call and no guarantee--yet. But researchers at the University of Pennsylvania have gotten us one step closer to relegating baldness to a thing of the past.

The university's reverse-balding process reactivates the genes, which usually function only in embryos, that stimulate skin cells to grow hair follicles. The team, led by George Cotsarelis, discovered during experiments with mice that when a mouse is wounded, its damaged skin can be induced not just to avoid forming scar tissue, but also to regenerate skin, complete with hair follicles and oil glands. The scientists tweaked the skin using wnt proteins long known to be involved in hair-follicle production.

"We have found that we can influence wound healing with 'wnts' or other proteins that allow the skin to heal in a way that has less scarring and includes all the normal structures of the skin, such as hair follicles and oil glands, rather than just a scar," Cotsarelis told the Independent, in the United Kingdom.

According to the article,

By introducing more wnt proteins to the wound, the researchers were able to double the number of new hair follicles. The research has implications that go beyond finding a cure for male-pattern baldness. It raises the possibility of treatments for acne, scalp conditions and hair overgrowth.

Since the early 1990s, scientists have known that skin can be stimulated to multiply hair follicles, but until now the process has worked only in a test tube. This has led to a competition to come up with the Holy Grail of hair: a molecular trigger to make this process happen in a living mammal.

Cotsarelis has cofounded a company, aptly named Follica, to develop the technology. It may take a while, but there could come a time when the famously bald will be bald no more. The list includes Jason Alexander, Yul Brynner, Kelsey Grammer, Andre Agassi, and Moby, just to name a few. Another famed baldy is comedian Larry David, who once said,

"Anyone can be confident with a full head of hair. But a confident bald man--there's your diamond in the rough."

Would David be as funny if he had a mop top? Would he be as confident if he had not had to overcome a shiny pate? Would his wife, Laurie, find him more or less attractive?

We may soon find out.

The bald facts (as listed by the Independent):

* More than 30 percent of men face balding before old age.

* Of the 100,000 strands of hair on the average head, at least 10,000 are in the process of dying.

* It takes up to six months for a follicle to produce a new hair.

* Male-pattern baldness is the most common: hair recedes from the temples, forehead, and crown. An excess of testosterone in the body is thought to be the cause.

* Effects of hair loss can be minimized by using hair thickeners to add body to remaining hair.

* Some specialists recommend massaging and stretching the skin of the scalp to promote blood flow to the follicles.

* Drugs used to treat baldness include Rogaine and Propecia. Both require a prescription and neither is available free on the NHS.

* Hair transplants are the most expensive solution, costing about $13,500 (£10,000).

---------------

Nature citation:

Mayumi Ito et al., "Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding," Nature 447, 316-320 (17 May 2007) Lett

Why Monkeys Can't Recite Shakespeare

A few years ago, Nobel laureate Sydney Brenner, a pioneer of genetics and a wit known for making wonderfully mischievous remarks, explained to me his theory about why humans have language. Grinning a Puckish smile, Brenner suggested that long ago, monkeys decided that talking got them into trouble, so they evolved to unlearn language. In contrast, we humans are less evolved because we gab on, getting ourselves into all sorts of awkward situations.

In reality, it appears that monkeys never troubled themselves with language at all. According to a research team led by Bing Su at the Kunming Institute of Zoology, in China, a single mutation in the KLK8 gene may have speeded up our ancestors' ability to learn and acquire language. KLK8 makes the neuropsin II protein, which is important for learning and memory.

The team discovered that humans have it, but monkeys don't--not even our close cousins the chimpanzees. According to an article at NewScientist.com,

KLK8 is the first human-specific discovery of a "splice variant"--a gene that is roughly the same in different species but is "cut and pasted" differently when it is expressed, resulting in proteins with new functions. Su's team have shown that KLK8 arose through a single mutation in DNA when a thymine nucleotide was exchanged for an adenine.

This small change had a huge impact, causing 45 additional amino acids to be loaded into the protein that the gene expresses.

In the language of genetics, this means that human intelligence may be based in part on a single "T" in genetic code being replaced by a single "A" in our ancestors three or four million years ago.

These single-letter variations are called single nucleotide polymorphisms (SNPs), a cumbersome term that lends credence to Brenner's "theory" about monkeys being smarter than us. They are not encumbered by such impenetrable phrases, developed by scientists, who sometimes seem intent on using their own KLK8 genes to create an ever more complicated language of their very own.

On the positive side, the KLK8 gene may have also contributed to the most beautiful forms of our language, as created by the likes of William Shakespeare. He wrote in Hamlet,

"What a piece of work is man! how noble in reason! how infinite in faculty! in form and moving how express and admirable! in action how like an angel! in apprehension how like a god! the beauty of the world, the paragon of animals!"

I wonder: would our cousins, the monkeys, agree?

Citation for article about the KLK8 gene in humans:
Human Mutation, DOI: 10.1002/humu.20547

Can Our Genes Save Us from Our Environment?

Why do some people end up with cancer, heart disease, or autism while others living under the same conditions don't?

Answering this is likely to consume the life sciences for most of this century as scientists tease out the intricacies of how environmental factors turn on and off genes. (See "Why Cancer Strike Some.") For instance, why is it that some people can be exposed to high levels of toxic chemicals, such as mercury, and remain healthy, while others suffer brain damage? More important, is there a single gene or multiple genes that protect some people from exposure to mercury? And if so, can this protector gene be used to develop methods for defending everyone against environmental scourges?

Two titans of life sciences at the National Institutes of Health (NIH) have decided that it's time we find out. In a Science article titled "Environmental Biology and Human Disease," Francis Collins and David Schwartz say that they believe the time has come to link two disciplines--environmental science and genetics--that have for too long operated as if they aren't related. Collins is director of the National Human Genome Research Institute (NHGRI), and Schwartz is director of the National Institute for Environmental Health Sciences (NIEHS). The two write,

Until recently ... the disciplines of environmental sciences and genetics have proceeded independently; investigators in the former discipline have focused primarily on adverse conditions and diseases that are etiologically driven by environmental factors (such as benzene-induced leukemia), and those in the latter field have been finding genetic factors for highly heritable conditions (such as cystic fibrosis). Progress is now being made in identifying common genetic variations that contribute to complex diseases such as age-related macular degeneration, type 2 diabetes, and prostate cancer. However, the best opportunity to reduce risk in genetically susceptible people for the foreseeable future will not be to re-engineer their genes, but to modify their environment.

("Modify their environment" is a curious way to put this; I'll get back to that in a moment.)

Collins and Schwartz call for a massive effort to record data about how, exactly, environmental factors impact genes and physiology. Part of this idea has already been launched with the Genes, Environment, and Health Initiative, which has a $40 million annual budget. "The near-term goal of the program is to develop new noninvasive tools and biomarkers for assessing individual exposures to environmental stressors that interact with genetic variation to result in human disease," write Collins and Schwartz. They suggest that biosensors be deployed to monitor individuals' exposure to everything from pesticides to cholesterol-rich foods. "However," they write, "to fully appreciate the predictive importance of these measures of exposure, this technology needs to be deployed in large-scale case-control and population-based genetic studies of health and disease."

The NIH loves big science projects, and this might be one of the biggest in history--and one of the most complex. It's a natural outgrowth of efforts such as the Human Genome Project on the genetics side and, on the environmental side, the National Children's Study, which, among other things, has been testing the impact of pollutants on kids.

This proposed fusion comes as global warming threatens to alter our environment and as human-produced chemicals are accumulating in the environment and in us. Last year, I was tested for 320 of these chemicals--everything from DDT to plasticizers--for an article in National Geographic, and I discovered that I have detectable levels of 165 of the chemicals. An obvious question is, what does this mean for me? Do I have genes that protect me from my rather high levels of bromide flame retardants, or are these chemicals that act as thyroid hormone disruptors slowly wreaking havoc on my physiology?

The two directors' choice of words in this regard is interesting: they say that "the best opportunity to reduce risk in genetically susceptible people for the foreseeable future will not be to re-engineer their genes, but to modify their environment." Modifying our environment is why you and I have these chemicals on board in the first place--and why diseases caused by junk food and other "modifiers" are raging.

We can only hope that the huge effort Collins and Schwartz are contemplating will shock us into realizing the real damage being done by such modifications to our bodies, cells, and DNA.

Making Music out of Genes

Listen to this.

It's the music created by the human protein thymidylate synthase A (ThyA). Really. At least, it's the notes created to "play" the music of this string of amino acids, with each amino acid assigned a chord.

Rie Takahashi, a graduate student at UCLA, dreamed up the idea of making music out of proteins when she read about a blind meteorology student at Cornell who converted the colors of a contoured weather map into tones corresponding to different hues.

Takahashi hopes her creation will help disabled geneticists "read" sequences using sound, she writes in a report in Genome Biology. "We wanted to be able to move away from a two-dimensional string of letters across a sheet of paper, and to see if adding another dimension--sound--would help," Takahashi told Nature.com.

Helping blind biologists "hear" DNA is laudable, but I'm also finding the notion of amino acids as chords strung together to be something eerie and wonderful, like putting my ear to a seashell and hearing the ocean. In addition, the idea makes sense, given that music is essentially digital--a series of precise calibrations of sound that the ancient Greeks thought of as a form of mathematics. For instance, the ancient Greek mathematician Pythagoras developed "The Music of the Spheres" to describe the proportional movements of the planets, moon, and sun in what he believed to be whole-number ratios identical to musical intervals.

Checking out Takahashi's Gene2Music website, I discover that other musically inclined scientists have applied notes and sounds to biological activities, such as the functions of a cell. You really need to check out these strange, compelling tunes.

Takahashi's website also allows you to enter any amino-acid sequence and have it translated into music. Try it, and listen to the slightly dissonant but curiously soothing sounds of protein sequences that are in a sense singing.