Is it Real, Or is it an Elaborate Computer Simulation?

Tim Hunt, Nobel Prize winner in biology, confronts two students in "systems biology" about the difference between "computer simulated biology" and real experimental biology in this video.

There is a very real gap between hands-on experimentalists and those who make their lives in the world of computer models and simulations. This is as true in biology as it is in climate, or in cognitive science. It is too easy for a computer modeler to believe that he has demonstrated something about the real world, when all he has done is generate a hypothetical output which obeys delineated constraints. As complex as the model may be, the real world is far more so. And the complexity of the model does not necessarily accurately reflect real world conditions.

The hope for the future of science lies with those who are cross-trained in both modeling and experimentation. They may be the only ones who will understand how to illuminate the way forward through an increasingly complex jungle of fractal realities.

Small RNA Gene Regulation

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The class of RNA known as "small RNA"--a subset of "non-coding RNAs"--is growing larger. Scientists are also growing more aware of the importance of this once obscure class of molecules, that apparently plays a critical role in regulating gene expression.

...molecular biologists have increasingly realized that many RNA snippets -- so-called small RNAs -- also directly influence which genes make proteins, and in some cases, how much protein. They've also found that some small RNAs play a unique role in protecting the integrity of genetic material.

..."It turns out that there are more types of small RNA molecules than anyone initially suspected," said Gregory J. Hannon, Ph.D., CSHL professor and pioneer in small RNA research. "And we are finding that each type that we discover acts in more ways than had previously been appreciated."

...Dr. Hannon and his collaborators are harnessing highly efficient new machines that determine the sequence of bases in millions of small RNA molecules simultaneously. They then scan the known genome to find matching sequences, as well as the sequences nearby. This original context is crucial to understanding why some snippets are chosen as regulators.

...Many RNA sequences, such as microRNAs, are flagged as regulatory molecules because they physically fold on themselves. Special proteins recognize the resulting double-stranded RNA, and chemically slice it to release regulatory RNA snippets.

The CSHL team found that double-stranded structures also form from "pseudogenes." Pseudogenes, in the past assumed to be useless "junk DNA," are damaged copies of normal genes left over from previous genetic events. The researchers found that RNA copies of normal genes sometimes pair up with copies from the related pseudogenes, resulting in double-stranded RNAs that -- far from being junk -- are able to activate the cell's regulatory apparatus. __ScienceDaily

The complexity of the small RNA systems of gene regulation is coming as something of a surprise to many biologists. These RNAs are part of a complex adaptive system which monitors and modifies gene expression according to rules that are so far poorly defined. As scientists utilise the increasingly powerful tools of systems biology, the long-held secrets of evolution on Earth are being teased out of the tangle.

It is no accident that the explosion of knowledge about genetic systems and control is occurring at the same time as the explosion of knowledge within information systems, and within systems in general. Without the micro-arrays, the sequencing tools, the computational hardware and software of bio-informatics, this work would be infinitely harder.

Pimp My DNA---Biology in the Digital Age

This is a nice accessible 1 hour Google Tech video that explains the impact of high speed automation and data analysis in biomedical research. If you want to better understand where the genomic revolution is heading, take a look. ( Via Eye on DNA)

The video includes an introduction to "Systems Biology", a dynamic new field in biology that promises to radically alter most of the things we think we know about biology. It also looks at the historical background of DNA science, at the state of the art, at DNA engineering, and at open source genomics.

Highly provocative and mind-stretching.

MicroArrays in Research: A Silent Revolution

A Micro-array is a potent tool of biological discovery, first used to study genetic variation, and now rapidly being adapted to a wide range of biochemical research. Briefly, micro-arrays incorporate a large number of biochemical probes onto a single chip, to allow up to thousands of simultaneous tests to be performed at once. Since humans are unable to process such large amounts of data quickly, micro-array data is processed by special "bio-informatics" data analysis packages. These tools together are driving a revolutionary change in what is possible to learn about complex biological systems.

Take embryonic stem cells (ESCs). Until recently, no one understood how ESCs could maintain the potential to develop into any cell type in the body. Recently, Israeli scientists used micro-arrays to track gene expression of ESCs as they developed into specialised cell types. They learned that ESCs must undergo complex patters of gene silencing to become particular types of cells and tissues.

Other scientists are using micro-arrays to track complex protein cell signaling pathways. Researchers at UT Austin have developed a microarray for testing proteins in saliva--for rapid, noninvasive diagnosis of heart attacks.

Scientists at Invitrogen Corp (NASDAQ:IVGN), have developed a micro-RNA (miRNA) microarray to test for the presence of the short RNA sequences that can influence tumour formation--as an early test for cancer, or even cancer potential.

Scientists in New York and Wisconsin may have stumbled upon a completely new approach to understanding Alzheimer's disease based upon results from microarrays looking at gene expression in the brains of specially bred mice and flies.

Scientists at the Cambridge Mass. startup Quanterix have developed high capacity protein testing micro-chips using sample wells only 2.5 microns in diameter, that are capable of detecting single molecules of a protein in a person's blood. Such chips should bring medicine closer to the holy grail of a quick, comprehensive "snapshot" of all the proteins active in a patient's system at any one time. (via Kurzweilai.net)

An entire field of biology, "Systems Biology" has grown up around such sophisticated tools of data acquisition--combined with complex tools of data analysis. These tools combined with the expertise of human minds to identify the significant findings among the masses of data, provide unprecedented power to biological researchers who are trying to eliminate some of the most burdensome diseases of modern life.

Update 14May08: Brian Wang has more on diagnostic microarrays here.

Genetic Engineering: Drew Endy's Edge Interview

Drew Endy is one of the young and edgy bio-engineers who as an MIT professor is shaping the next generation of bio-engineers to be even edgier. Dizzy times? Even dizzier times coming!

Programming DNA is more cool, it's more appealing, it's more powerful than silicon. You have an actual living, reproducing machine; it's nanotechnology that works. It's not some Drexlarian (Eric Drexler) fantasy. And we get to program it. And it's actually a pretty cheap technology. You don't need a FAB Lab like you need for silicon wafers. You grow some stuff up in sugar water with a little bit of nutrients.

...in 2003 I taught a course at MIT, the Synthetic Biology Lab with some colleagues, and we had 16 students. For the last four years this course has been doubling every year, and it's now taught independently at about 60 schools in 30 or 40 countries worldwide, it's called IGEM, the International Genetically Engineered Machines competition. There are teams of teenagers from Germany programming DNA happily there, as well as Australia, Russia, Japan, China. The competition was won by the team from Peking University this year, and six or seven hundred students participated....How do you recognize this exponential and serve it and bring more people to participate in it?

...the previous generation of people working in biotechnology are scientists, and the ones coming up now are engineers. We're going to have to invent our new world of biotechnology and I suspect we'll learn lessons around biological safety from the past generation, but all the other lessons are up for grabs. The bio-security framework is going to collapse. The IT framework based on patents isn't going to scale, and the questions of playing God or not are so superficial and embarrassingly simple that they're not going to be useful in discussion.

There are some people who understand what's going on, and who are in a position, or who have comfort acting on time scales that are relevant. It is interesting for me to learn how difficult it is for folks to appreciate what an exponential technology really implies. The fact that sequencing goes from approximately zero to human genomes in ten years. The same thing is happening with construction of genomes. And with the parts collection—the standard biological parts doubling every year. And the same thing is happening with the number of teenagers who would like to do genetic engineering; it's doubling every year. How do you actually live in a world where you're surfing that exponential in a way that's constructive and responsible? Very few people get that.___Edge.org

Anyone trying to predict the future beyond the next 5 or 10 years in bio-medicine, bio-energy, bio-weapons, bio-nanotech, etc. is clearly at a disadvantage. Because there is absolutely no way of knowing what this djinn is going to do, now that it is out of its bottle.

New technology is allowing the talented and skilled youth of today and tomorrow entry into worlds of power and performance previously limited to only a few. The need for wise oversight and guidance has never been greater.

Bacterial Genome Transplanted, Next Step--Synthetic Organism?

After replacing DNA in mycoplasma capricolum organism with the chromosome from mycoplasma mycoides, scientists at the Ventner Institute are planning work on a completely synthetic organism.

Scientists at the J. Craig Venter Institute (JCVI), a genomics research facility, transplanted a bacterial chromosome from one type of bacteria into another, and have completely replaced an entire bacterial genome and its expression. The work of Carole Lartigue, Ph.D. and colleagues was published in the latest issue of Science:

The JCVI team devised several key steps to enable the genome transplantation. First, an antibiotic selectable marker gene was added to the M. mycoides LC chromosome to allow for selection of living cells containing the transplanted chromosome. Then the team purified the DNA or chromosome from M. mycoides LC so that it was free from proteins (called naked DNA). This M. mycoides LC chromosome was then transplanted into the M. capricolum cells. After several rounds of cell division, the recipient M. capricolum chromosome disappeared having been replaced by the donor M. mycoides LC chromosome, and the M. capricolum cells took on all the phenotypic characteristics of M. mycoides LC cells.

As a test of the success of the genome transplantation, the team used two methods -- 2D gel electrophoresis and protein sequencing, to prove that all the expressed proteins were now the ones coded for by the M. mycoides LC chromosome. Two sets of antibodies that bound specifically to cell surface proteins from each cell were reacted with transplant cells, to demonstrate that the membrane proteins switch to those dictated by the transplanted chromosome not the recipient cell chromosome. The new, transformed organisms show up as bright blue colonies in images of blots probed with M. mycoides LC specific antibody.

The group chose to work with these species of mycoplasmas for several reasons -- the small genomes of these organisms which make them easier to work with, their lack of cell walls, and the team's experience and expertise with mycoplasmas. The mycoplasmas used in the transplantation experiment are also relatively fast growing, allowing the team to ascertain success of the transplantation sooner than with other species of mycoplasmas.

According to Dr. Lartigue, "While we are excited by the results of our research, we are continuing to perfect and refine our techniques and methods as we move to the next phases and prepare to develop a fully synthetic chromosome."

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Synthetic biology is one of many approaches to studying the mechanisms of life. Craig Ventner says that he will create an organism that will solve the energy crisis. Perhaps he will. As long as western civilisation survives the onslaughts of anti-enlightenment thinking, I suspect that organisms that can produce unlimited energy will be the least of achievements from synthetic biology, nano-biology, biologic computing etc.

Because western educational systems do not teach students to use their broad intellectual capacities, most humans--even in the developed world--do not have a clue about the multiple revolutions in scientific discovery that are teetering on the very brink of the activation energy hump. Some students of the singularity believe that the true revolution will require the creation of a friendly superhuman machine intelligence.

Personally, I believe that machine augmentation of human intelligence will be enough--once humans learn to use the intellects they possess. But since the educational establishments are incapable of helping humans learn about their intrinsic capacity, there may be some delay.