Seminar report on " BIOLOGICAL COMPUTERS "

Biological computers are special types of microcomputers that are specifically designed to be used for medical applications. The biological computer is an implantable device that is mainly used for tasks like monitoring the body's activities or inducing therapeutic effects, all at the molecular or cellular level.

The biological computer is made up of RNA (Ribonucleic Acid - an important part in the synthesis of protein from amino acids), DNA (Deoxyribonucleic Acid - nucleic acid molecule that contains the important genetic information that is used by the body for the construction of cells; it's the blue print for all living organisms), and proteins.
 

Advantages

The main advantage of this technology over other like technologies is the fact that through it, a doctor can focus on or find and treat only damaged or diseased cells. Selective cell treatment is made possible.

The biological computer can also perform simple mathematical calculations. This could enable the researcher to build an array or a system of biosensors that has the ability to detect or target specific types of cells that could be found in the patient's body. This could also be used to carry out or perform target-specific medicinal operations that could deliver medical procedures or remedies according to the doctor's instructions.

This not only makes the healing process easier. It also allows the doctors to focus only on the damaged, diseased or cancerous cells found in the patient's body without causing stress to other and normal cells.

How its works

Biological computers are made inside a patient's body. The researchers or doctors merely provide the patient's body with all of the necessary information or a "blueprint" along which lines the biological computer would be "manufactured." Once the "computer's" genetic blueprint has been provided, the human body will start to build it on its own using the body's natural biological processes and the cells found in the body.

As of today, reading signals produced by cell activity is not yet possible due to technological limitations. However, through the use of a tiny implantable biological computer, these cellular signals could easily be detected, translated and understood using existing medical and laboratory equipment.

Through boolean logic equations, a doctor or researcher can easily use the biological computer to identify all types of cellular activity and determine whether a particular activity is harmful or not. The cellular activities that the biological computer could detect can even include those of mutated genes and all other activities of the genes found in cells.

As with conventional computers, the biological computer also works with an output and an input signal. The main inputs of the biological computer are the body's proteins, RNA, and other specific chemicals that are found in the human cytoplasm. The output on the other hand could be detected using laboratory equipment.

Applications

The implantable biological computer is a device which could be used in various medical applications where intercellular evaluation and treatment are needed or required. It is especially useful in monitoring intercellular activity including mutation of genes.

In the lab, we have many interesting and ingenious ways of looking at biological processes. The biotech revolution has allowed us to develop methods for detecting and quantifying molecules produced by living cells; we can detect gene expression and activity, and we can pinpoint within a cell the precise location of proteins. However, while these tasks are relatively easy to perform in vitro on a lab bench, imagine the benefits to medicine if we could apply them in vivo (in a whole, living animal). Nanotech machines could be injected into a patient that would then monitor for certain conditions and  responding accordingly

There is a paper, published online today in Nature Biotechnology, that brings this dream a little bit closer to reality. Scientists at Harvard and Princeton have detailed the construction of a biological circuit that uses siRNA to affect boolean logic statements. The circuit works by having two different mRNA strands that code for the same protein but contain untranslated regions that correspond to different siRNA sequences.

Different endogenous inputs will control the expression of the various siRNAs, thereby affecting which of the two mRNA strands gets expressed; an example would be inputs A and B targeting one mRNA, and inputs X and Y inputting the other mRNA, thereby giving the logic expression (A AND B) OR (X AND Y). Other mRNA strands can be designed to work for (A AND NOT B), and so on. The output of the mRNA strand that isn't silenced can be a reporter protein: luciferase or GFP, for example.

Although this research describes relatively simple artificial molecular machinery, it doesn't take much imagination to see the potential. Biological machines can be implanted or even built within a patient's own cells that will act as biosensors, watching out for disease markers. Should they find such markers, the molecular logic circuits like this could chose the most appropriate action. That could involve inducing programmed cell death in the case of cancerous cells or synthesis of a drug in specific tissues. Obviously such therapies remain vaporware for now, but that won't remain true for much longer.

Biocomputers constructed entirely of DNA, RNA and proteins can function inside the body as "molecular doctors," according to Harvard’s Yaakov “Kobi” Benenson, a Bauer Fellow in the Faculty of Arts and Sciences’ Center for Systems Biology.

“Each human cell already has all of the tools required to build these biocomputers on its own,” says Harvard’s Benenson. “All that must be provided is a genetic blueprint of the

machine and our own biology will do the rest. Your cells will literally build these biocomputers
Benson and colleagues claim to demonstrate that biocomputers can work in human kidney cells in a culture. Also, they have developed a conceptual framework by which various phenotypes could be represented logically. Phenotypes are characteristics that are measurable and that are expressed in only a subset of the individuals within that population (like blond hair and brown eyes)

Using a biocomputer as the calculation mechanism, researchers could build biosensors or medicine delivery systems that could single out specific cell types in the body. These molecular doctors could target only cancerous cells, for example, ignoring healthy ones.

Biomolecular computers have been proved in concept by researchers at the Weizmann Institute of Science; see the article Biomolecular Computer    

Dr. Leonard Adleman, a computer scientist at USC, discussed the possiblity of biocomputers as early as 1994. Science fiction fans didn't have to wait so long; they could read about the intellectual cells in Greg Bear's 1984 novel Blood Music:
His first E. coli mutations had had the learning capacity of planarian worms; he had run them through simple T-mazes, giving sugar rewards. They had soon outperformed planaria...

Removing the finest biologic sequences from the altered E. coli, he had incorporated them into B-lymphocytes, white cells from his own blood...Using artificial proteins and hormones as a means of communication, Vergil had "trained" the lymphocytes in the past six months to interact as much as possible with each other and with their environment - a much more complex miniature glass maze.

For a scientist who has just staked a claim to the first programmable and autonomous biological nanocomputer, Professor Ehud Shapiro is remarkably low-key when asked to predict how such research may eventually change the world.

He refuses to get drawn into detailed discussions of futuristic applications for the technology, and prefers to leave prophesying to others. At the same time, his incremental approach to the embryonic science of turning DNA into trillions of tiny computers, swimming inside a test tube, has given Shapiro a keen sense of direction as he embarks upon a long-term mission.

Shapiro does not see his computer as a potential competitor to silicon-based electronic computing, as some have suggested. Instead, he envisions DNA computers as a "molecular computing device that can operate initially in a test tube and eventually inside an organism and interact with its biochemical environment."

DNA computing could possibly be used to streamline laboratory analysis of DNA, by eliminating the need for sequencing. This, he said, could happen within a decade.

"In the longer term, you may have medical applications in which this device can operate in vivo, inside a living organism," he says. "Based on the information it receives from the environment and medical knowledge encoded in the software it may diagnose the problem and prescribe a solution, and then it could synthesis that molecule and output it."

That's as far as Shapiro is willing to venture on the prospects of the technology.
"I don't have an opinion on nanogurus or nanoapproaches," he says dryly during an interview in his office at the Weizmann Institute of Science in Rehovot, Israel. "We know where we are and where we are going to go. It's just going to be a very long way."

The starting point for Shapiro, who recently published his design for a molecular computer in Nature magazine, came after his Internet software company called Ubique

Plotting a path back to academia, Shapiro stumbled upon research being done in molecular computing, and challenged Yaakov Benenson, a biochemistry Ph.D. student, to help make it work. Their modest initial goal was to find a way to use turn DNA into the most elementary mathematical computing device known as a finite automaton, capable of answering "yes" or "no" to very basic questions about a bunch of zeroes and ones.

"We constructed a molecular realization of this mathematical device," Shapiro says. "It has input, it has software and it has hardware components; and when it computes it produces output, which is another molecule."

To do this, Shapiro and his colleagues used the four components of a DNA strand known as A, C, G and T to encode the zeroes and ones and create an input molecule with an exposed "sticky" end. Then, another DNA strand -- the software -- swoops in to try and hook up with an exposed edge like a Lego piece attempting to lock into a complementary block. Each exposed edge has a specific complementary DNA strand.

After hooking up, the hardware gets to work. An enzyme called ligase seals the link, and another called Fok-1 moves in to snip the strand, leaving the next section exposed.

The process continues several times until the computer delivers an answer to the question. There are 765 different possible software programs that can be used for simple calculations, such as whether there are an even or odd number of zeroes or ones.

Shapiro's research is the latest step forward in a field founded by Leonard Adleman of the University of Southern California, Los Angeles. In 1994, Adleman proved that DNA could compute, when he used the stuff to solve the "traveling salesman" problem, in which the shortest route between several cities must be mapped without going through the same city twice.

Conventional computers have extreme difficulty solving the problem, especially when dealing with many points on a map. This is because electronic computers are based on sequential logic, which makes them good at solving a problem requiring lots of computations in a row. But posed with a puzzle of how to figure out the shortest route between 100 cities -- a problem best cracked by simultaneously performing an enormous number of short operations -- conventional computers do not make the grade. Adleman demonstrated that DNA could be an efficient way to solve such problems.

Shapiro says his DNA computer is fundamentally different from Adleman's breakthrough. Although Adleman's computer was composed of many trillions of tiny DNA molecules swimming around in a test tube, Shapiro says it was essentially a large operation that required active involvement of scientists.

"The calculation needed to be carried out by humans. In our case, the computer is just the molecules," says Shapiro, who can put a trillion of his own biological computers into a drop of solution. "His computer is measured in meters, ours is measured in nanometers."

Experts point out that Shapiro faces stiff competition and will be challenged to scale up the work to perform more complex computations.

John Reif, professor of computer science at Duke University, described Shapiro's work as "ingeniously constructed experiments" that clearly demonstrated the ability to perform simple computations via solid experimental protocols.

"But there is a lot of competition out there in the DNA computing world," he added, singling out DNA computing research at Princeton University and the University of Wisconsin that has gone beyond the finite automaton.

"People are really aggressively pushing the limits, so the challenge for the Israelis is to go in and push those limits as defined by some of those strong competitors," Reif said.
Shapiro has no illusions. The biggest stumbling block now is the dependency on natural enzymes, meaning scientists must search for the right enzymes that could help perform computations on DNA. Science still has no clue how to create designer enzymes that could pave the way to dramatic progress.

For his part, alongside the finite automaton, Shapiro has taken an important theoretical step forward by building a model of a molecular Turing Machine, which is a representation of a computing device capable of an infinite number of computations. It is in this green, squarish model, sitting in a cardboard box in his office, that Shapiro sees the real potential for molecular computing. The ability to create a molecular Turing Machine would allow scientists to use DNA to generate massive computing power. In the meantime, he is keeping focused on the scientific challenges ahead -- and plans to be tied up in his DNA strands for a while. "We have made a first small step in this direction," he says. "I believe this will keep me busy until I retire."

Biocomputers constructed entirely of DNA, RNA and proteins can function inside the body as "molecular doctors," according to Harvard’s Yaakov “Kobi” Benenson, a Bauer Fellow in the Faculty of Arts and Sciences’ Center for Systems Biology.

“Each human cell already has all of the tools required to build these biocomputers on its own,” says Harvard’s Benenson. “All that must be provided is a genetic blueprint of the machine and our own biology will do the rest. Your cells will literally build these biocomputers for you.”

Benson and colleagues claim to demonstrate that biocomputers can work in human kidney cells in a culture. Also, they have developed a conceptual framework by which various phenotypes could be represented logically. Phenotypes are characteristics that are measurable and that are expressed in only a subset of the individuals within that population (like blond hair or brown eyes).

In theory, using a biocomputer as the calculation mechanism, researchers could build biosensors or medicine delivery systems that could single out specific cell types in the body. These molecular doctors could target only cancerous cells, for example, ignoring healthy ones.

Dr. Leonard Adleman, a computer scientist at USC, discussed the possiblity of biocomputers as early as 1994. Science fiction fans didn't have to wait so long; they could read about the intellectual cells in Greg Bear's 1984 novel Blood Music:

His first E. coli mutations had had the learning capacity of planarian worms; he had run them through simple T-mazes, giving sugar rewards. They had soon outperformed planaria...

Removing the finest biologic sequences from the altered E. coli, he had incorporated them into B-lymphocytes, white cells from his own blood...Using artificial proteins and hormones as a means of communication, Vergil had "trained" the lymphocytes in the past six months to interact as much as possible with each other and with their environment - a much more complex miniature glass maze.

Biocomputers constructed entirely of DNA, RNA and proteins can function inside the body as "molecular doctors," according to Harvard’s Yaakov “Kobi” Benenson, a Bauer Fellow in the Faculty of Arts and Sciences’ Center for Systems Biology.

“Each human cell already has all of the tools required to build these biocomputers on its own,” says Harvard’s Benenson. “All that must be provided is a genetic blueprint of the machine and our own biology will do the rest. Your cells will literally build these biocomputers for you.”

Benson and colleagues claim to demonstrate that biocomputers can work in human kidney cells in a culture. Also, they have developed a conceptual framework by which various phenotypes could be represented logically. Phenotypes are characteristics that are measurable and that are expressed in only a subset of the individuals within that population (like blond hair or brown eyes).

Using a biocomputer as the calculation mechanism, researchers could build biosensors or medicine delivery systems that could single out specific cell types in the body. These molecular doctors could target only cancerous cells, for example, ignoring healthy ones.

Dr. Leonard Adleman, a computer scientist at USC, discussed the possiblity of biocomputers as early as 1994. Science fiction fans didn't have to wait so long; they could read about the intellectual cells in Greg Bear's 1984 novel Blood Music:

His first E. coli mutations had had the learning capacity of planarian worms; he had run them through simple T-mazes, giving sugar rewards. They had soon outperformed planaria...

Removing the finest biologic sequences from the altered E. coli, he had incorporated them into B-lymphocytes, white cells from his own blood...Using artificial proteins and hormones as a means of communication, Vergil had "trained" the lymphocytes in the past six months to interact as much as possible with each other and with their environment - a much more complex miniature glass maze.
(Read more about Greg Bear's intellectual cells)