Will we domesticate biotechnology in the next 50 years? More than 150 years of spectacular advances in physics, chemistry, and computing have thoroughly transformed the way we live. Yet so far, the big revolutions in molecular biology have had their impact primarily on professional laboratories, not our everyday lives. What do we need to do in order to domesticate biotech?
Physicist Freeman Dyson recently explored this question:
"Will the domestication of high technology, which we have seen marching from triumph to triumph with the advent of personal computers and GPS receivers and digital cameras, soon be extended from physical technology to biotechnology?"
Dyson predicts this will happen in the next 50 years:
"I predict that the domestication of biotechnology will dominate our lives during the next fifty years at least as much as the domestication of computers has dominated our lives during the previous fifty years."
What form might this domestication take? Among Dyson's suggestions for domestication is user-friendly genetic engineering for hobbyist plant and animal breeders. I'm not so sure that making genetic engineering idiot-proof is the major hurdle; in fact, genetic engineering today is somewhat of an oxymoron. We may be able to engineer pet fish to express a green fluorescent protein, but we honestly have no clue how to engineer any but the most simple, monogenic traits.
We will dometicate biotechnology, and I predict that this will happen in two ways: by bringing biotech into the day-to-day practice of medicine, and by bringing genetic engineering to a truly sophisticated level, on par with aerospace engineering.
Bringing Biotech into the Clinic
To be honest, with the exception of imaging technology, medicine as practiced today is extremely low-tech. Very few of the fancy techniques that scientists use in a molecular biology lab are available on a routine, affordable basis in the clinic. Blood tests are downright primitive. And in spite of all of our sophisticated genome analysis technology, detailed genotyping is almost never used in medicine. Biotech is ripe for domestication in the clinic.
Dirt Cheap Genome Sequencing
One day, every newborn child will be routinely genotyped; that is, the hospital lab will take a blood sample and, quickly and cheaply, determine that baby's DNA sequence in the millions of places where humans can differ. Our genotype will become part of our medical records, which of course we ourselves will also have access to. Genotyping can be used to customize drug and disease treatments, as well as suggest lifestyle choices that will help avoid or minimize diseases that a person may be susceptible to. Universal genotyping can even be used by family history hobbyists.
The technological barriers will soon be overcome, leaving the social ones remaining as the largest obstacle to universal genotyping. Who can have access to this information? How much do you really want to know about your disease susceptibility? Your paternity? These aren't trivial questions.
The Universal Blood Test
High-tech, preventative diagnostics will transform the way we practice medicine. Most of today's diagnostic tests, with the exception of medical imaging, are based on decades-old techniques. Leroy Hood, a founder of Seattle's Institute for Systems Biology is working on technology for affordable, routine blood tests that will provide a comprehensive picture of your health, including the very early detection of diseases like cancer. These blood tests, one day cheap enough to be done annually, could thoroughly modernize preventative medicine.
Real Genetic Engineering
At Boeing, engineers can essentially design a new plane completely by computer, and predict in minute detail how that plane will behave in real-world weather. True genetic engineering will mean being able to make such quantitative predictions with the cell, but currently our abilities to make quantitative predictions are embarrassingly small. Analogous to Boeing's computer-aided design, computer aided genetic engineering will one day enable us to develop gene replacement therapies that don't have cancer as a side effect, develop specific, side effect-free drugs that treat tough diseases, and develop microbes that can generate energy from renewable resources, clean up toxic spills, or perform chemical reactions that organic chemists haven't yet been able to achieve.
The first step towards achieving this level of sophistication will be to completely understand all of the parts of an organism; the next will be to understand how those parts work as a system. We've nearly reached that first step for a eukaryotic organism: brewer's yeast, one of biology's key model organisms, will have an essentially completely annotated parts list within the next 10 years or so. Many scientists are now struggling with the next step, trying to make sense of how these parts work as a system. Yeast will be the first Boeing 747 of biology - an organism that we can completely and predictively model by computer, without extensive trial and error studies in the lab.
Maybe, after we've really learned how to do genetic engineering, hobbyists will then fulfill Dyson's dream of user-friendly plant design, and come up with a way to make glow-in-the-dark roses.
Tuesday, August 21, 2007
Sunday, August 19, 2007
The Politics of God in the NY Times Magazine
The NY Times Magazine today has cover piece arguing that while the West may have figured out how to largely separate politics and religion, the rest of the world is unlikely to follow:
"Countless millions still pursue the age-old quest to bring the whole of human life under God’s authority, and they have their reasons."
If that's really true, we can expect that modern science will be a phenomenon largely confined to the West, with the rest of the world using science, pioneered elsewhere, to build more hi-tech weapons.
Perhaps though, the case is overstated in the NY Times piece - Japan and Korea have relatively secular politics, and a correspondingly strong scientific infrastructure. Several modernizing nations, such as India and China, are working hard to build their scientific reputations; to do so requires some commitment by their respective goverments to separate ideology from the political decision making process. The young Chinese and Indian graduate students, coming in droves to the US for a scientific education, will inevitably make life better in their non-Western home countries when they return.
The next step is to figure out how to get young Iraqis, Jordanians, Iranians, and Africans to come seeking a scientific education in the US.
"Countless millions still pursue the age-old quest to bring the whole of human life under God’s authority, and they have their reasons."
If that's really true, we can expect that modern science will be a phenomenon largely confined to the West, with the rest of the world using science, pioneered elsewhere, to build more hi-tech weapons.
Perhaps though, the case is overstated in the NY Times piece - Japan and Korea have relatively secular politics, and a correspondingly strong scientific infrastructure. Several modernizing nations, such as India and China, are working hard to build their scientific reputations; to do so requires some commitment by their respective goverments to separate ideology from the political decision making process. The young Chinese and Indian graduate students, coming in droves to the US for a scientific education, will inevitably make life better in their non-Western home countries when they return.
The next step is to figure out how to get young Iraqis, Jordanians, Iranians, and Africans to come seeking a scientific education in the US.
Tuesday, August 14, 2007
Ancient Microbes Revived from Antarctic Ice May Be Spreading Their Genes
After being encased in Antarctic ice for 8 million years, ancient microbes thawed by a team of researchers revved up their metabolic engines again and began making proteins and replicating. These are the oldest organisms ever brought back to life after a deep freeze.
The research team, a group primarily from Rutgers, looked at the microbial population in some of the oldest ice known on earth, obtained from Antarctica’s Beacon Valley. Using microscopy, the researchers could see that these samples had a variety of bacteria encased inside. But microscopy can only tell you so much; to learn more, the research team turned to DNA sequencing.
The standard way of identifying what you have in a mixed population of bacteria is to sequence the 16S ribosomal DNA - a gene encoding an important component of the protein-synthesizing machinery. This gene is plays such an important functional role that it changes very slowly over evolutionary time, thus allowing scientists to easily compare DNA sequences among organisms that have diverged from each other for hundreds of millions of years. The 16S rDNA sequences from these ice samples revealed nearly a dozen different types of bacteria in the 8 million-year-old ice; that’s not much compared to a fresh, modern sample of seawater, but that's great for very old ice.
Some of these ancient bacteria were alive. When the researchers melted the ice (but keeping it still cold and dark - these are sensitive bacteria), they found that at least some of the bacteria were able start up their metabolism, which was measured using radioactive metabolites that the bacteria could ingest and incorporate into their protein or DNA.
16S rDNA can tell you what kinds of bacteria you have, but another intriguing question is what genes do these bacteria have? Are most of their genes similar to those of today’s known bacteria? After sequencing as much of the bacterial genomes as they could, the researchers found that a substantial 46% of the genome sequence did not match any known genes. This is not actually so surprising - in spite of all of the DNA sequence from thousands of organisms stored in GenBank, we know that we have sampled only a fraction of the different types of genomes on earth. The genomes of multicellular organisms are relatively similar to each other, but that bacterial world represents a vast, poorly explored genetic resource. We know most of the genes on our planet are in fact missing from our databases; we best understand the biology of that small subset of bacterial and archaebacterial genes that was present in the ancestors of all eukaryotic organisms.
While scientists may not know much about most bacterial genes, evolution is not blind to them. Bacteria are remarkably generous with their genes; they pass them on not only to their descendants, but to their neighbors as well. This phenomenon of lateral gene transfer, or LGT, makes the evolutionary analysis of bacteria fiendishly difficult. The authors of the ice microbes paper raise another fascinating (or depressing, if you study bacterial evolution) possibility: that ancient ice is a “gene popsicle,” facilitating gene transfer not only across species, but also across time. With the onset of an ice age, microbes, harboring a given set of genes, get preserved for thousands or millions of years, until the ice melts. That’s when these ancient bacteria return to the local ecosystem, where they can pass on their ancient genes via LGT to modern bacterial species. These modern species then, with luck, use these recently revived genes to better adapt to their environment. As the authors of the paper put it:
“Our analysis suggests that melting of polar ice in the geological past may have provided a conduit for large-scale... LGT, potentially scrambling microbial phylogenies and accelerating the tempo of microbial evolution.”
This is a mind-boggling prediction, which will be difficult to test without a lot more bacterial genome sequencing. However, the idea again demonstrates the tremendous resources evolution has to work with. As the biologist Leslie Orgel reportedly once said, “Evolution is cleverer than you are.”
The research team, a group primarily from Rutgers, looked at the microbial population in some of the oldest ice known on earth, obtained from Antarctica’s Beacon Valley. Using microscopy, the researchers could see that these samples had a variety of bacteria encased inside. But microscopy can only tell you so much; to learn more, the research team turned to DNA sequencing.
The standard way of identifying what you have in a mixed population of bacteria is to sequence the 16S ribosomal DNA - a gene encoding an important component of the protein-synthesizing machinery. This gene is plays such an important functional role that it changes very slowly over evolutionary time, thus allowing scientists to easily compare DNA sequences among organisms that have diverged from each other for hundreds of millions of years. The 16S rDNA sequences from these ice samples revealed nearly a dozen different types of bacteria in the 8 million-year-old ice; that’s not much compared to a fresh, modern sample of seawater, but that's great for very old ice.
Some of these ancient bacteria were alive. When the researchers melted the ice (but keeping it still cold and dark - these are sensitive bacteria), they found that at least some of the bacteria were able start up their metabolism, which was measured using radioactive metabolites that the bacteria could ingest and incorporate into their protein or DNA.
16S rDNA can tell you what kinds of bacteria you have, but another intriguing question is what genes do these bacteria have? Are most of their genes similar to those of today’s known bacteria? After sequencing as much of the bacterial genomes as they could, the researchers found that a substantial 46% of the genome sequence did not match any known genes. This is not actually so surprising - in spite of all of the DNA sequence from thousands of organisms stored in GenBank, we know that we have sampled only a fraction of the different types of genomes on earth. The genomes of multicellular organisms are relatively similar to each other, but that bacterial world represents a vast, poorly explored genetic resource. We know most of the genes on our planet are in fact missing from our databases; we best understand the biology of that small subset of bacterial and archaebacterial genes that was present in the ancestors of all eukaryotic organisms.
While scientists may not know much about most bacterial genes, evolution is not blind to them. Bacteria are remarkably generous with their genes; they pass them on not only to their descendants, but to their neighbors as well. This phenomenon of lateral gene transfer, or LGT, makes the evolutionary analysis of bacteria fiendishly difficult. The authors of the ice microbes paper raise another fascinating (or depressing, if you study bacterial evolution) possibility: that ancient ice is a “gene popsicle,” facilitating gene transfer not only across species, but also across time. With the onset of an ice age, microbes, harboring a given set of genes, get preserved for thousands or millions of years, until the ice melts. That’s when these ancient bacteria return to the local ecosystem, where they can pass on their ancient genes via LGT to modern bacterial species. These modern species then, with luck, use these recently revived genes to better adapt to their environment. As the authors of the paper put it:
“Our analysis suggests that melting of polar ice in the geological past may have provided a conduit for large-scale... LGT, potentially scrambling microbial phylogenies and accelerating the tempo of microbial evolution.”
This is a mind-boggling prediction, which will be difficult to test without a lot more bacterial genome sequencing. However, the idea again demonstrates the tremendous resources evolution has to work with. As the biologist Leslie Orgel reportedly once said, “Evolution is cleverer than you are.”
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