Posts Tagged ‘DNA’

Technology is moving faster than our ability to take decisions

Wednesday, January 8th, 2014 by Roberto Saracco
Will we end up "designing" a new born DNA? Credits: image on the Technology Review article referenced in the text

Will we end up “designing” a new born DNA? Credits: image on the Technology Review article referenced in the text

I recently read a nice article on Technology Review stimulating thinking on the implication of technology progress in the area of pre-natal screening based on genomics.

I stumbled upon it (it was published in December last year) when preparing for a talk I am giving today to a school class on the evolution of technology and its impact on biz. Often, the questions I get are not on the technology itself, nor on the biz but they are related to ethics and are an indicator of a latent, hidden, fear about something we really don’t know.

The technology evolution is sometimes, and for some, exciting. At other times it may be scaring, even for those who are potentially tech-wise. What I noticed, to some surprise, is that most of the fears come from youngsters whilst elderly people seem more fascinated by evolution.

However, most of the time I perceive uneasiness when confronted to technology evolution because of potential “damages” produced by technology, be it an increasing usage of energy, increasing (potential) pollution (many times I hear of people scared by electromagnetic pollution) or be its implication on how social life evolves (digital divide, increasing isolation with loss of face to face interaction…).

Although all these fears are real and need to be addressed (I am stating that the fears are real not that they are grounded on reality per se) I feel that the real challenges ahead are in our difficulty in evolving our ethical framework to cover what the evolution of technology makes possibile. And this is where the article I read is interesting. It does not provide “solutions” but it pearly points at challenging issues.

It cannot provide solutions, because we are not in a domain where the problem is how much 2+2 is, nor how to build an earthquake resistant building. We are talking about a common feeling of ourselves as a Society.

Till the 1900 there were no ethical issues about prolonging life a a person in a coma. Quite simple we had no power in that area. But as technology has progressed we can now prolong life in a coma patient almost indefinitely. And we can prolong life with organ transplant or with specific cure. All of this raises ethica issues that simply were not there before.

I was flabbergasted by discovering that over 50% of medical cost in the USA is incurred to better/prolong the life in the last six months of people’s life. 50% is a very big portion of the overall cost, and one can wonder how much health care improvement we could obtain by dedicating just half of that to take care of the other parts of life.

Often we say that we do not have the right of unplugging the life cord keeping a patient alive but do we realise that by making that choice  aren’t we basically deciding to not help people in need because of the lack of money?

I am not saying this is right or wrong, I am just pointing out that there are issues that are very difficult to tackle.

What about the increasing knowledge we have on genomics? We can sequence the genome (at a lower an lower cost) of a foetus and we can spot genomic defects that lead to syndromes like Down, Edwards, … Patau. This required an invasive procedure, amniocentesis, to get a few cells from the foetus to look at (into) the chromosomes but now it is becoming possible to get the same information by looking at the foetal RNA present in the mother blood.

We can expect in the coming years to be able to much more information by a complete sequencing of the foetus genome and hence to identify many other potential anomalies. Yes, I wrote “potential” because we are far from being able to associate to several genetic diseases a certain correlation with some genomic anomalies. We know that alteration to the BRCA1 gene strongly increases the risk of breast cancer but it is not a sure thing. Similarly, the presence of an extra X chromosome in males (XXY instead of XY) -Kleinfelter syndrome- often does not result in perceivable syndrome letting the person live a “normal” life. Would a foetal detection of these anomalies lead parents to be to terminate the pregnancy. And besides: what is normal?

Parents with achondroplasia, a condition leading to dwarfism, would elect to terminate a pregnancy of a foetus that does not show the genetic modification leading to dwarfism because they would rather have a child like they are?

Knowing about the genome anomalies is for sure a benefit since it would allow doctors to take early measure to correct issues like in phenylketonuria whose bad effects can be avoided by an appropriate diet from birth and many others. On the other hand this knowledge opens the door to eugenics with dramatic ethical implication. Are children with green eyes “not normal”? Or with black hair? What about girls? In India, China and to some extent South Korea the knowledge about the sex of the foetus has increased abortion…

Again, I am in no position to take a stand in the matter, although I can tell the whites from the blacks but there are so many greys I cannot tell apart! I just notice the tremendous complexity that our increase in knowledge in the technology domain creates and the difficulty in addressing such a complexity.

I can just say, IMHO, that technologists should acknowledge this and involve people with specific understanding of non technological aspects in the application of the technology. In a way, this is what we are doing at the IEEE, Future Direction Committee when looking at Smart Cities made possible by technology evolution by involving sociologists that can help in assessing the “desirability” of technology application from a human point of view.

DNA goes to Silicon Valley …

Saturday, September 14th, 2013 by Roberto Saracco

Few years ago professors at Harvard and MIT published a manifesto calling for cross fertilisation in science. They observed that over the last 300 years Science has become more and more specialised. This has led to amazing results and to the discovery of very specific approaches in each scientific field. With the manifesto the professors claimed that the time has come to take advantage of the progresses in each discipline by applying them to other. The resulting cross fertilisation would allow faster progress in all fields.

Indeed, this is what’s happening.

Graphene growth: This image, taken using atomic force microscopy, shows graphene nanoribbons aligned in intersecting rows atop a silicon wafer. Researchers used DNA to synthesize and position the ribbons. Credits: Stanford University

Graphene growth: This image, taken using atomic force microscopy, shows graphene nanoribbons aligned in intersecting rows atop a silicon wafer. Researchers used DNA to synthesize and position the ribbons. Credits: Stanford University

As a point in case take this news from Technology Review reporting on the approach taken by researchers at Stanford to create graphene ribbons that can be used to make transistors.

Graphene, a single atom layer of carbon, has a much better conductivity than silicon, which means the potential to build electronic components using much less power, and that in turns means less dissipation, higher density, more capacity.

To create transistors, however, you need a material, such as silicon and germanium, that has a clear distinction of states, one where current flows and the other where there is very little or (ideally) no current. This is called band gap.

Unfortunately graphene has a very small band gap, hence it is not suitable for transistors making.

Scientist, however, have observed that ribbons of graphene, 10 nm wide, have a good band gap, sufficient to make a transistor. The problem is how to make such ribbons and deploy them exactly where you want them to be.

Here is where the researchers at Stanford took advantage of bioengineering. They laid strands of DNA in the geometry required (DNA strands are “big, measuring in µm) and have them absorb copper atoms. Then they exposed this geometry to methane and hydrogen gas at hot temperature. This led to the creation of graphene ribbons of the desired size and in the required place. They were not perfect, some ribbons was thicker than one single atoms but they were ok for the job.

We are still very far from developing a chip with transistors made of graphene, the technology that has been developed and perfected over these last 50 years in chip manufacturing is so far unbeatable but what draw my attention was this cross fertilisation in the making. We are still in the research domain but so was the case of the transistor back in the early fifties (after having been created in the 1947). It took silicon more than 20 years to become a chip … Consider that today0s pace of evolution is slightly faster than it was sixty years ago and you see that predicting a graphene chip in the next decade is not science fiction.

DNA has to go in the Cloud

Friday, August 16th, 2013 by Roberto Saracco
This is what the output of a DNA sequencer looks like...

This is what the output of a DNA sequencer looks like…

The cost of sequencing DNA decreases every day and the speed of sequencing increases. This is leading to an overload of data that gets more and more difficult to process.

The sequencing process does not yield information that is directly useful. It provides raw sequences that need to be processed to derive information, and this requires a lot of processing power, a processing power doctors do not have.

This is the alarm bell rung by researchers at the John Hopkins Hospital.

According to the researchers the sequencers produce something similar to what you get when you through a newspaper into a shredder. Plenty of fragments that are unreadable and extremely complex to reassemble (that is the purpose of a shredder, so no complain there).

The solution they are pursuing tackles two fronts: on the one hand better algorithms for sequencing so that the resulting material requires less computation and more processing power by using many computers in parallel.

For the latter they are going to rely on Cloud Computing and they are specifically considering Amazon for a low cost and powerful computation service.

Amazing to think how much processing has moved into the commodity area. Who would have imagined just few years ago than researchers on the evolution edge would seek support from Amazon?

A new kind of computer: you!

Saturday, April 6th, 2013 by Roberto Saracco
A XOR gate that can be performed inside a cell.

A XOR gate that can be performed inside a cell.

Our bodies are made up by hundreds of billions of cells and now researchers at Stanford have managed to create a (sort of) computer that goes inside a cell and uses molecules available in the cell itself for performing computations.

Any computer has to carry out three basic operations: store data, transmit data and process data. The Stanford team made the news last year by succeeding to perform the first two operations using cellular processes and molecules. Now they have announced in a paper, published on March 28th on Science, to have succeeded in implementing the third missing part: create a functioning processing unit within the cell.

The basic processing unit in a computer is a XOR logic gate. If you can do a XOR operation you can do any other operation you can dream of. If you want to dig into the properties of XOR and how to combine it to perform any kind of processing you can read the explanation on Wikipedia.

You can see the basic scheme of this “processor” on the left. What the researchers did was to find out a way to use DNA and RNA to create this logic gate. They have called this a “transcriptor”, and it is a sort of biological transistor. It works using a well calibrated mixture of enzymes, and the researchers have chosen those that can be found normally in bacteria and other living cells so that indeed this transcriptor can operate inside a living cell.

A very weak signal that may not lead to the activation of a gene when processed by the transcriptor gets amplified (similarly to what happen in a transistor that amplifies and electrical signal) and therefore can activate the gene(s).

According to the researchers this transcriptor can be used to assess the presence of certain compound in a cell, and remember it for later use, it can tell a cell, on command, to produce a certain protein by activating a specific gene and so on. Actually, they claim the the range of applications is so broad that it is impossible to be defined by a single group and this is why they have opened up the results of their work by placing it in a public domain to let other teams to further polish the method and come up with other applications.

Why DNA has been chosen by Nature ?

Wednesday, January 30th, 2013 by Antonio Manzalini

DNADNA is the well known macro-molecule with a double helix, encoding all genetic information in a language with 64 three-letter words built from an alphabet with a set of four different letters. The used symbols are A, C, G, T and mean adenine, cytosine, guanine and thymine (thymine T is replaced by uracil U in RNA). Since the discovery of the molecular structure of DNA in 1953, by Watson and Crick, a lot of progresses have been made in studying the ensembles of molecular structures of the genetic code.

Scientists are investigating why this special language has been chosen by Nature.

As we have read in the last post there are effort for mimicking this language in informatics:    an avenue towards DNA-based computing and bioinformatics. On this matter, let me go back again to symmetry.

DNA has two helices, which run anti-parallel to each other: this is an inherent symmetry, which is highly important in the replication process of DNA. Furthermore, they say that the genetic code has an exact A-G permutation symmetry and an almost exact T-C permutation symmetry with respect to the third nucleotide. Given the enormous importance of spontaneous symmetry breaking in several physical phenomena, these symmetries in the genetic code are even more amazing!

In 1993 this paper proposed explaining the degeneracy of the genetic code as the result of a symmetry breaking process. This can be can be compared with explaining of the positioning of the chemical elements in the periodic table as a consequence of an underlying dynamical symmetry (which, in turn, are reflected in the electronic shell structure of atoms). Have a look at this recent paper to read more details about this fascinating perspective. Universal characteristics of symmetry breaking are even here, in the language of Nature.

Since the discovery of DNA huge progresses have been made in unveiling the genetic code, and the rate of discoveries in this field is accelerating day by day thanks also to the growing amounts of processed genetic data: a multi-disciplinary approach capable of integrating Mathematics, Physics, Biology, Informatics and Engineering could bring to a breakthrough, changing profoundly ICT horizons.

A powerful programming language: the DNA

Tuesday, January 29th, 2013 by Roberto Saracco

This is the century of the Brain, at least this is what many scientists claim, but this decade is the decade of the genome. We (they) have been able to improve the sequencing process at a rate faster than the Moore’s law and the expectation is to be able to sequence a full genome in less than an hour at a cost of less than 100$ by the end of this decade.

Schematics of a DNA strand

Schematics of a DNA strand

This will create a big data base with millions of genomes that can be analysed for understanding how variation in the genome can lead to problems and diseases. And here comes the point: harvesting a tremendous amount of data and increasing our knowledge is good but in order to have an impact on our well being we need to be able to manipulate the genome to fix issues and also to increase its capabilities. Although this latter seems a second order priority (and clearly creates ethical issues) this is what is happening right now and what we will see increasing in this decade.

There are already several techniques for splicing, that is for introducing specific genes inside a chromosome. It is thanks to them that we have been able to create bacteria producing methane or bacteria eating oil to fight pollution in the ocean after an oil spill. However, today, splicing is very difficult.

Hence, the interest for this news from MIT and researchers of the Rochester University.

Researchers are proposing to use a natural bacterial protein and RNA able to recognise and cut viral DNA to produce a component, called Cas9 that binds to RNA sequences. These can target specific location in the genome and cut the DNA in that location.

Once the DNA strand is cut it can be recombined without a certain gene or a new gene can be inserted. In other words, rather than attacking the problem of changing the DNA itself researchers are proposing to use RNA as a tool for doing that.

With this approach one can easily program the DNA to instruct for production of any protein, like inserting a subroutine into a program.
The RNA complex is very precise: only an exact match with the DNA location will cause the cutting. The “power” of this programming language is not the variety of basic instructions (there are only 4 symbols that are assembled in triplets) but the billions of already written programs that have been tested through hundreds of millions of years in the field and finely tuned!
We can expect by the end of this decade to see many programmers at work, although when you ask them if they are using Pyton or older languages like C++ they will answer: I use RNA and DNA and it works pretty well!

Suppose you need to store something and retrieve it 10,000 years later…

Thursday, January 24th, 2013 by Roberto Saracco

Well, of course, the first thing coming to mind is that it is unlikely that you get to be blamed if the storage can no longer be read (or if you do you likely don’t care!).

However, our world is becoming more and more described through bits and with the present storage media they are unlikely to survive even 100 years. Compare this to the masterpieces from painters or writers. Can you imagine a world without a Van Gogh or Shakespeare heritage? Indeed, if Van Gogh and Shakespeare have chosen (not that they could) to store their masterpieces in jpg or doc files we won’t be able to enjoy them today.

Comparison of DNA vs MagTape cost taking into account the cost of writing with DNA and the time of content life

Comparison of DNA vs MagTape cost taking into account the cost of writing with DNA and the time of content life

Scientists have been working on this issue, that is becoming ever more pressing since today we have reached a digital store in the ZB figure. What can be used to preserve digital information forever (or at least 10,000 years)?

Just knock on Nature’s door.

Researchers at the EMBL-European BioInformatics Institute have succeeded in finding an effective way to write DNA code to store information.

The DNA is a very robust way to store information, we can read the DNA of animals that got extinct long ago, 10s and 100s thousands year ago.

With all the advances we had in the last decade reading DNA sequences has become easy and cheap. What has remained very difficult is to write specific sequences of DNA since the number of errors during the writing procedures are too high.

The researchers at the EMBL-EBI have succeeded in developing a technique that is much more robust so that even 4 consecutive errors can be intercepted and recovered.

Do not expect, however, to get rid of your hard disc anytime soon to replace it with a DNA cup, even though that cup would be able to store over 100 million hours of hd video.

As it is shown in the graph, the cost is still very high, and it needs to decrease at least a hundred folds to become competitive with a magnetic tape. But of course, cost reduction is what we have become used to in ICT!

Tagging molecules …

Thursday, September 27th, 2012 by Roberto Saracco

Science is progressing through painstaking observation and measurements. This started in the XVI century and continues today. We have invented amazing and ingenious ways to observe and measure the universe and the tiniest particle. Any new “tool” increasing our observation and measurement capability is bound to open up new discoveries and out of them new applications to our daily life…

Florescent colour particles attach to DNA strands

Hence, I was interested in reading the news that scientists have invented an extremely effective way to discover what molecules are present in a cell (or any other minute aggregation) and how they connect one another.

To observe molecules in a cell researchers have to disseminate in the cell fluorescent particles that binds to specific molecules. Each particle can only bind to a specific molecule so that if one observes a “red” dot that means the presence of a specific molecule.

The problem with this approach is that one can only detect as many molecule types as there are different coloured particles. Unfortunately we only have three-four colours max to play with and therefore it is only possible to detect simultaneously only four different types of molecules.

This is where the invention of the researchers of the Wyss Institute for biologically inspired engineering at Harvard comes handy.

They have found a way to attach coloured particles to DNA strands, thus permitting to create an almost infinite set of patterns that can be detected. This solves the problem of observing many different types of molecules at the same time.

You may want to take a look at the paper to grasp the full details.

What matters to me is that this is another step in the direction of learning more about our cells, how they are composed at the molecular level and how they work. This is important as we are moving to the genomic era of medicine and need to understand the finely tuned steps that make life tick and that sometimes go astray. Because if we understand that we are on our way to fix problems.

Clearly, this additional understanding will pass through the manipulation of big data. Consider that a liver cell (to take just an example) contains about 8 billion protein molecules and you see what I mean.

HI-C: looking at the DNA structure

Thursday, March 22nd, 2012 by Roberto Saracco

DNA: a fractal globule

It looks like a ball of thread, but, mathematically speaking, it is a very special ball: a fractal globule. And it represent the DNA forming a chromosome.

So far we have been used to see the DNA as “the double helix”  a ribbon containing the pairs with the code of life. Now scientists have managed to look at the real 3D structure of the DNA forming the chromosome and have discovered that the ribbon is bended and wrapped to form a sort of sphere, but a very particular one. You might expect it. The various portions of the “ribbon” need to be readily accessible to be copied and this requires that the ribbon part you are interested in is visible. This would not be the case in a normal ball of threads, but this is exactly what happens in fractal globules.

In spite of the very complex appearance, as shown in the figure, each portion of the ribbon can be easily isolated and once used can return to its original position in the ball. It is not knotted (in a way it is similar to the Peano curve).

The result was obtained by researchers from the Broad Institute (Harvard and MIT) and has been published in the Harvard Gazette. To discover the structure of the DNA in the chromosome the researchers have used a new probing technique, HI-C, that basically measure the number of collisions among atoms. Nearer atoms are likely to bounce up more frequently and this is certainly the case for atoms in nearby places on the DNA ribbon. However, there the researchers have discovered many places of high bouncing for atoms that in principle should have been quite distant from one another in the DNA ribbon. By computing the distance in terms of bouncing frequency the researchers have been able to construct the structure of DNA, and it turns out that it is a fractal globule.

What I think is interesting is to notice how processing of data can reveal the inner structure of our world, beyond what is the physical limits of optics. It is sort of magic: detecting quantities and being able to derive meaning out of that. GEt ready to see much more along this lines in our Digital Societies. Data are really at the core of everything.

A USB Memory Stick? No, it’s a genome sequencer!

Thursday, March 8th, 2012 by Roberto Saracco

Several times in this blog I posted news showing the acceleration of the technologies for sequencing the human genome. The target is to arrive by the end of this decade with every one of us (most of us) having in his pocket his genome sequence. To achieve this result the sequencing should become cheaper (down to 100 euros) and faster (like a blood analyses).

A USB Stick for Molecular analyses

This is “just” another one, but it really shows that we are on track. This USB device is able to detect DNA molecules, not sequencing the whole genome but once you plug it in in a laptop and you wire together twenty of them you will be able to sequence a whole human genome in … 15 minutes! That’s amazing.

The device is produced by Oxford Nanopore. They will begin selling this USB sequencer at the end of 2012 at a price of 900$.

Just think of the implications. A machine like this would be able to cut dramatically the price of genome sequencing (may be not down to 100 euros but surely well under 1,000 – you need to factor in the cost of the reagents required). Besides, its speed can make the sequencing a normal procedure. Just remember that the first genome sequencing took 10 years and several billion $.

I can see the time, soon, when we will have our genome in our medical record and drugs being prescribed base on the genome. Plus, proactive medicine will take into account the likelihood of suffering from certain diseases and would let us monitor for early tell tale signs and prompt action.

There will also be, as in any new technology, issues on privacy and potential misuse. Still, it is a new exciting frontier to explore!