Biology Enters 'The Matrix' Through New Computer Language

ScienceDaily (July 25, 2008) — Ever since the human genome was sequenced less than 10 years ago, researchers have been able to access a dizzying plethora of genomic information with a simple click of a mouse. This digitizing of genomic data--and its public access--is something that would have been unthinkable a generation earlier.

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But as molecules go, DNA is pretty straight forward. With its simple composition and linear structure, it easily lends itself to mathematical models. Not so with proteins. In fact, proteins are an order of magnitude more complex than DNA. It is proteins, not DNA, that carry out the cell's heavy lifting. However, with their intricately folded three-dimensional shapes determining a seemingly endless range of possible functions and their manifold interactions with other proteins and with DNA,

the leg-work required to mathematically capture the protein universe seems absurd.

And it is.

That is why a team of Harvard Medical School researchers have decided to attack this issue from an entirely new angle. Rather than build a mountain range of proteomic data one grain of dirt at a time, they have developed a computer program that can take on the responsibility of assembling such a gargantuan model.

Enter Little b, a computational language that can penetrate the "mind" of a cell.

"Through incorporating principles of engineering, we've developed a language that can describe biology in the same way a biologist would," says Jeremy Gunawardena, director of the Virtual Cell Program in Harvard Medical School's department of systems biology. "The potential here is enormous. This opens the door to actually performing discovery science, to look at things like drug interactions, right on the computer."

Most current computational methods of modeling biological systems are not unlike writing a document with pen and paper. Each new project starts from scratch; there are no facilities for cutting and pasting, for linking to other texts, for including images, etc.--things that come so "naturally" to electronic documents.

Harvard Medical School researcher Jeremy Gunawardena, a mathematician by training, teamed up with Aneil Mallavarapu, a cell biologist and computer scientist, to lead a project that would bypass these limitations.

"We knew that the secret to doing this would be to assimilate fundamental concepts of engineering, concepts like modularity and abstraction, into the biological realm," says Mallavarapu, who was recently awarded the Merrimack prize by the Council for Systems Biology in Boston for developing this program.

Modularity involves breaking a problem down into separate modules and constructing each module so that it can interact with the others. Abstraction refers to extracting generic biological properties and incorporating them into the modules, so that they can use this abstract information in concrete contexts. Put another way, abstraction means that, unlike the old days of pen and paper, each new model does *not* need to be built from scratch. Models can be built upon each other and their individual modules refined and re-used.

To do this, Mallavarapu used the programming language LISP, a language widely used in artificial intelligence research. LISP is famous among computer scientists due to its ability to write code that, in turn, can write code, enabling a programmer to derive new mini-languages.

"LISP isn't like typical programs, it's more like a conversation," says Gunawardena. "When we input data into Little b, Little b responds to it and reasons over the data."

For example, Gunawardena's lab works on kinases, a kind of protein that transfers phosphate chemicals to other proteins in order to regulate their activity. While this property is common to all kinases, there is a great deal of variety in how particular kinases carry this out. Little b, however, understands this basic property of kinases, this abstraction.

Here, the researchers demonstrated how they were able to interact with Little b to build complex models of kinase activity, using Little b as a kind of scientific collaborator, and not simply a passive tool.

On a larger scale, the researchers also used the program to query the development of fruit fly embryos. As a result, they discovered levels of complexity in these embryonic structures that previous research had missed.

"This language is stepping into an unknown universe, when your computer starts building things for you," says Gunawardena. "Your whole relationship with the computer becomes a different one. You've ceded some control to the machine. The machine is drawing inferences on your behalf and constructing things for you."

The researchers sometimes admit, half-joking, that Little b sometimes feels a little bit like "The Matrix"--referring, of course, to the film trilogy in which human beings lived in a computer-generated virtual world.

Mallavarapu and Gunawardena have a pretty clear vision for this project: they want every biologist in the world to use it.

But in order to bring the program out from the early adopter community, where it is currently being used by colleagues in the Harvard community, it needs to be more accessible.

"The next step is to create an interface that's easy to use," says Gunarwardena. "Think of web page development. Lots of people are creating web pages with little or no knowledge of HTML. They use simple interfaces like Dreamweaver. Once we've developed the equivalent, scientists will be able to use our system without having to learn Little b."

And the more people use it, the smarter it gets. As researchers around the world input their discoveries into Little b, the program will assimilate that information into its language.

The ultimate goal is to have an in silico, virtual cell--a dynamic biological system living in software.

"Sure, it's a long way off," says Gunawardena, "but we're getting there."

This research was funded by the National Institutes of Health and Harvard Medical School. The funding and data sources for this study had no role in study design; in the collection, analysis, and interpretation of data; and in the writing of the report.

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Journal reference:

1. Aneil Mallavarapu, Matthew Thomson, Benjamin Ullian, and Jeremy Gunawardena. Programming with models: modularity and abstraction provide powerful capabilities for systems biology. Journal of the Royal Society Interface, online publication, July 23, 2008

Adapted from materials provided by Harvard Medical School.

Source: Harvard Medical School. "Biology Enters 'The Matrix' Through New Computer Language." ScienceDaily 25 July 2008. 29 July 2008 .

A national DNA database could bring justice

Ethical questions over police use of DNA || DNA of innocent people should not be kept by police || Should DNA database extension plans have been rejected? BBB Forum

Samples of triumph

A national DNA database could bring justice to thousands of families; our only concern should be over the way it is compiled.

James Randerson

Articles

November 2, 2006 1:45 PM

Roy Linzee Tuthill, or Tutts to his friends, was saving up for a bicycle. So, on 23 April 1968 he decided to hitch back home from his school in Chessington, Surrey instead of taking the bus. It was his last journey.

The 14-year-old's body was found three days later. He had been sexually assaulted and strangled. His clothing was found folded neatly and lain across his body.

For 33 years Tutts' killer remained free, until the police picked up Brian Lunn Field (by then aged 66) for drink driving. His DNA matched a sample from the crime scene and in 2001 he was given a life sentence for the killing.

This is the jaw-dropping, humbling power of DNA - a tiny speck of human being that can reach back into history and place a man at a crime scene beyond almost all doubt.

Last year 20,000 people were brought to justice with the help of DNA including the perpetrators of 422 murders and manslaughters, 645 rapes and 9000 domestic burglaries. Countless others have had their innocence affirmed by the technique.

This is science at its most triumphant service of justice.

But what have we given up for this success? DNA fingerprinting is only as good as the database holding the profiles of "suspects". And Britain has by far the most police-friendly laws governing whose DNA profiles go on the national DNA database.

Over 3 million of us are on it including many who have never even been charged with a crime - 51,000 of them are children. Last week the prime minister advocated extending the database to cover everyone.

With so many of us on the database have we handed over too much power to the police? Critics of the database argue that it fundamentally changes the relationship between the state and the citizen. By being on it we are all somehow under constant surveillance. We are transformed from citizens to suspects.

It's an anxious-sounding rhetorical flourish, but what does this actually mean?

What difference does being on the database make if you haven't done anything wrong?

Consider the worst-case scenario. Your DNA profile is on the database and your DNA is found at a crime scene. You are not the villain, but you cannot establish an alibi for the night in question. The police have no other evidence to link you to the crime (because you didn't do it).

If the case gets to court, what can the presence of DNA tell the jury? Simply that you (or your identical twin) visited the crime scene at some time, along with several other people whose DNA was found there. The police would be reckless or desperate to try to get a conviction on that evidence alone.

How is this different from the current situation in which you are wrongly identified by a witness? In this case the state has made you a suspect even though you haven't done anything wrong.

We are all potential suspects in a police investigation as it is. The DNA database doesn't change that one jot. The fact that the police have your DNA profile on file doesn't mean you are being watched by an always-on CCTV camera.

Most of the time the database is blind to your existence. If the proper safeguards against misuse are in place, it is only if your DNA is found at a crime scene that you have some explaining to do.

There are important questions of civil liberties here, but they concern the unfair way in which the database is put together. Currently we have a classic British fudge. The man on the street is, in the eyes of the law, exactly the same as the woman who has been arrested but released uncharged - they are both innocent. Yet her DNA is placed on the database and his is not.

The way the database is compiled at the moment has resulted in a massive over-representation of men on the database, and an even bigger skew towards black men - 37% are on the database.

The way to solve this inequity is for everyone's DNA to be placed on the database at birth.

If we accept that "innocent" people sometimes commit crimes then there is no good reason why innocent people who happen to wind up in a police station should have their DNA taken, but the rest of us don't.

Roy Tuthill's family waited 33 years for justice. Had DNA fingerprinting and a comprehensive database been available in 1968 finding Tutt's killer would have been much easier.

I challenge anyone who would defend the right not to have their DNA profile stored on a computer for use solely in crime-fighting to explain why that nebulous freedom carries more weight than the chance of justice for thousands of families.

This week, the Nuffield Council on Bioethics, an independent group that examines developments in medicine and biology, launched a public consultation into the ethical issues surrounding the UK's National DNA Database.

Debating ethics of DNA database

Debating ethics of DNA database

By Iain Haddow BBC News

The DNA samples of the guilty and innocent are kept on the database

The scientist who pioneered genetic fingerprinting says he's concerned that the personal data of innocent people is being wrongly held by police.

Professor Sir Alec Jeffreys told the BBC the retention of thousands of innocent people's DNA raised "significant ethical and social issues".

He was speaking as the government launched an inquiry into the way the national DNA database is used.

Per capita, it is the world's largest database and holds the DNA profiles of 4.5m people. The equivalent system in the US, known as CODIS, and run by the FBI, contains over five million DNA profiles.

When first launched in 1995, only the DNA of convicted criminals were kept by police. But following a change in the law in 2001, all DNA collected by forensics - for whatever purpose - can be stored permanently.

Innocent and guilty on database

That ranges from people who voluntarily give police a DNA swab in order to eliminate themselves from investigations - to convicted rapists and murderers.

Since 2004, the data of everyone arrested for a recordable offence in England and Wales - all but the most minor offences - has remained on the system regardless of their age, the seriousness of their alleged offence, and whether or not they were prosecuted.

The database contains the DNA of criminals and a whole number of people who've...never even been charged with a crime. Roger Smith, Justice

Such is the controversy surrounding the database that last September one of England's most senior appeal court judges, Lord Justice Sedley, called for

the database to be made compulsory for all UK residents as well as visitors to Britain.

At the time he said the current system was "indefensible".

'PR gimmick'

His call has been echoed by the law reform group Justice, which described the consultation as a "public relations gimmick".

DNA PROFILING Deoxyribonucleic acid (DNA) is found in virtually all cells Only a tiny sample of saliva, blood, semen, etc, is needed for testing At the molecule's core is a long sequence of chemical units, which is checked for a gender and 10 other 'markers' Probability of a chance match is less than one in one billion A match may be with a specific individual or hint at a relative Profiles can provide indications of ethnic origin They do not point to genetic disorders or susceptibilities

Justice's Director, Roger Smith, said:

"The national DNA database should either list those guilty of a crime or everybody in the country.

"At the moment, it contains the DNA of criminals and a whole number of other people who have attracted the interest of police officers but never been convicted - in many cases, never even charged - with a crime."

Recently, Home Office Minister Tony McNulty said

the database had helped police solve as many as 20,000 crimes a year.

Institutional racism

But according to the government's own figures, the database contains the genetics of a disproportionate number of ethnic minorities.

Forty per cent of black men in the UK have their DNA stored on the database and there are concerns that it could be open to abuse.

Black men are disproportionately targeted right across the criminal justice system where there is no evidence that they disproportionately commit crime Ali Dizaei, National Black Police Association

The president of the National Black Police Association, Chief Superintendent Ali Dizaei, said, "Black men are disproportionately targeted right across the criminal justice system where there is no evidence whatsoever that they disproportionately commit crime.

"We see the current data as a classic example of institutional racism."

Professor Sir Bob Hepple, who until December was Chair of the Nuffield Council on Bioethics, said: "Young black males are over-represented on the National DNA Database. This may have arisen from policing practices and the disproportionate arrest of certain ethnic groups."

But he said:

"The establishment of a population-wide forensic DNA database cannot be justified at the current time. The potential benefits would not be great enough to justify the cost and intrusion to privacy."

A population-wide forensic DNA database cannot be justified...The potential benefits would not justify the cost and intrusion to privacy. Sir Bob Hepple, former Chair, Nuffield Council on Bioethics

Geneticist Sir Alec Jeffreys first found a way to identify people through their DNA by accident at the University of Leicester two decades ago.

He said he welcomed an inquiry into public attitudes to the database and how it is developing.

"The national DNA database is a very powerful tool in the fight against crime," he said.

"But recent developments such as the retention of innocent people's DNA raises significant ethical and social issues."

Balancing rights and safety

The government consultation will be conducted by the Human Genetics Commission advisory body.

The retention of innocent people's DNA raises significant ethical and social issues Professor Sir Alec Jeffreys, Geneticist, University of Leicester

Over the next six weeks, it will hold sessions with dozens of members of the public

in an exercise costing £75,000.

The conclusions will be fed back to the government in a report next year on the forensic use of DNA.

The man in charge of the inquiry Human Genetics Commission chairman Sir John Sulston said:

"There is an important balance to be struck between individual rights and public safety and we need to know how people feel about these issues".

Should the UK introduce a universal compulsory, or voluntary, national DNA Database? What ethical issues would it raise?

Should everyones DNA record be held on a National Database? What are the ethical considerations? What do you think?

Calls for expansion of the UK's DNA database


DNA in depth || Debating ethics of DNA database || Has our DNA database gone too far? || All UK 'must be on DNA database'

Mandatory DNA database rejected

Both killers were convicted with compelling DNA evidence

There are no plans to extend the DNA database to contain information from all people, the Home Office has said.

Calls for its content to be made universal have followed the conviction of two murderers using DNA evidence.

Suffolk serial killer Steve Wright and Sally Anne Bowman's murderer, Mark Dixie

were both captured because their DNA was taken after unrelated offences.

But the Home Office said a mandatory database "would raise significant practical and ethical issues".

The DNA database, which covers England and Wales, currently contains around 4.5m profiles - routinely taken from criminal suspects after most arrests.
7% of UK adult population

However, it could be threatened when European judges are asked to rule next week on a test case of two Britons who want their details removed from the database.

The applicants say their human rights have been infringed by the decision to leave their details on the database, despite the fact that they had never been found guilty of a crime.

Debate call

Steve Wright's profile was on the system after being convicted of theft in 2003.

When police found his DNA on the bodies of some of his victims they matched it with his profile.

But Mark Dixie was not on the system at the time of Sally Anne Bowman's murder.

It was only when he was arrested for assault after a fight in a bar that his DNA was taken and he was linked to the murder.

He was arrested within five hours.

Det Supt Stuart Cundy, who led the murder hunt, said: "It is my opinion that a national DNA register - with all its appropriate safeguards - could have identified Sally Anne's murderer within 24 hours.

"Instead it took nearly nine months before Mark Dixie was identified and almost two and a half years for justice to be done."

The Association of Chief Police Officers (Acpo) is also calling for a debate on the issue.

'Vital role'

The Chief Constable of Lincolnshire, Tony Lake, speaks for the association on DNA.

He said: "If there was a national database of everybody then we would solve more crime, of that there is absolutely no doubt.

"In the conviction of Steve Wright - and today of Mark Dixie - you've heard about the vital importance that DNA played. But any database that we hold has to be reasonable and proportionate in the eyes of the public."

The statement issued by the Home Office said: "There are no government plans to introduce a universal compulsory, or voluntary, national DNA Database and to do so would raise significant practical and ethical issues."

The Times estimates if the two applicants succeed in their EU bid to have their records removed, 13% of the profiles on the database may have to be destroyed.

The pair, from Sheffield, had their DNA taken after they were arrested in 2001, but charges were not pressed.

They asked for their data to be removed from the DNA database but this was refused.

They are appealing on the grounds that Article Eight of the European Convention on Human Rights, the right to respect for private life, and Article 14, the prohibition of discrimination, have been violated.

We owe it to the victims - DNA Databases

reposted from Guardian

We owe it to the victims

The DNA database could make it impossible to get away with serious crime in this country. It's an opportunity we shouldn't pass by.

James Randerson

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September 6, 2007 11:31 AM | Printable version

Thirty-seven murders, 16 attempted murders, 90 rapes.

If you do not believe that every UK resident and visitor to our shores should have their DNA profile stored on the UK's police National DNA Database these are the figures you have to argue against. These are the numbers of victims and families of victims you have to look in the eye and say: "An 'innocent' individual's freedom not to be on the database is worth more than the closure you got from seeing your child's killer put away for life."

The figures above are just the most serious of the more than 3,000 that have been solved since 2003 using a match on the DNA database to people who were arrested by the police but never charged, let alone convicted. All of these 3,000-plus crimes were perpetrated by people who were "innocent" in the eyes of the law, yet their presence on the database gave the police decisive leads - sometimes in stone-cold cases that were years old.

And these convictions are just a taste of what the database might achieve if more people were on it. The most recent figures state that there are 3,865,429 people on the database and 382,746 profiles from crime scenes. The vast majority of profiles on the database are still from convicted criminals with just 139,463 arrestees or volunteers on the database in November 2005. Since May 2001, 182,612 DNA profiles found at crime scenes have been matched with 165,099 separate perpetrators. Some of these crimes may well have been solved eventually using more traditional policing methods, but the DNA database gives the police a powerful hotline to people who do despicable things.

The senior appeal court judge Lord Justice Sedley is right to say that the current arrangements - in which arrestees who are never changed can have their DNA taken by the police (by force if necessary) - are "indefensible". There is no reason why the man arrested at a climate change demonstration but not charged should be treated differently from the woman walking in the park. Both are innocent in the eyes of the law but his DNA profile is added to the database while hers is not. This unfairness has given us a database that is heavily skewed towards men and black people - 37% of black men are on the database compared with 9% of white men.

Of course, the right safeguards must be in place to make sure profiles are only used to catch criminals and that misuse by unscrupulous officials or police is impossible. But from here we can go one of two ways. Either society decides that only convicted criminals - who have given up their rights - are kept on the database. Or we decide collectively that the gains in terms of catching murderers and rapists are important enough for the rest of us to give up the freedom not to be on the database.

We have an opportunity to make it nearly impossible to get away with serious crime in this country. Could you really look into the eyes of those victims' families and say that freedom is worth more?

The DNA database proposal threatens civil liberties, is unlikely to prevent violent crime

reposted from Guardian

The end of idealism

If technology - such as the DNA database - keeps presenting short-term fixes to social problems, we will have no incentive to build a better society.

Mark Braund

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September 8, 2007 12:00 PM | Printable version

There are many reasons why Lord Justice Sedley's call for mandatory DNA sampling should be firmly opposed, most were well rehearsed in the comments following James Randerson's post yesterday.

But even if someone could persuade me that the ends (detecting and punishing serious crime) justify the means (a further considerable incursion into the civil liberties of law abiding citizens), and that it was feasible to compile and maintain such a database, I would have grave reservations for another reason.

Technological advances are increasingly delivering supposed solutions to all manner of social and economic problems. In this case,

advances in DNA technology hold out the possibility that all those culpable for serious crimes could be brought to justice.

The problem with such technology-inspired fixes is that they generally only tackle the symptoms of complex social problems, rather than engaging with, and addressing, the root causes.

If you believe that all murderers, rapists and other violent criminals are born evil, and were always going to offend, whatever their experience of life as youngsters, then the promise held out by a mandatory DNA database will probably strike you as the ultimate weapon in the struggle against violent crime.

If, on the other hand, you think there's more to it; that a fair proportion violent offenders turn to crime at least in part because of some avoidable aspect of their early years experience, and that their criminality is not therefore inevitable, then you should consider carefully the implications of the DNA database proposal.

If you will permit me a moment of idealism: one conclusion of the unfolding process of social evolution would, presumably, be a society without crime. Movement towards this goal is dependent on our gaining a better understanding of the causes of certain individuals turning to crime, and on our generating the political will to address those causes once identified.

Over the last few decades, despite the promises of politicians ("Tough on crime, tough on the causes of crime.") we have largely given up investigating and trying to address root causes in favour of reactionary quick fixes which are often no fix at all.

If we were to rely on an expanded DNA database to deliver justice, we would have even less incentive to strive to improve society by tackling the environmental factors that contribute to people becoming violent criminals. We would doubtless celebrate our achievement in developing technology that enabled us to catch and punish all murderers and rapists, but the crimes would still be committed and the victims and their families would still endure unimaginable pain.

Would it not be better to direct our efforts towards measures that might help to reduce the incidence of violent crime in the first place? Pre-emptive justice is surely preferable to the retributive justice we settle for today.

You might argue that the existence of a DNA database would act as a deterrent. But I'm not sure that even a cast-iron guarantee of being caught would make much difference. Most serious offenders are as indifferent to their own fate as they are to that of their victims.

Technological advance has a similarly disincentivising effect in other spheres. Instead of addressing the economic factors which leave many millions of people hungry in a world that produces more than enough food to go around, we invest huge sums in developing technologies like genetic modification, which, while providing short-term relief in certain circumstances, do nothing to tackle the underlying causes of food scarcity.

The DNA database proposal threatens civil liberties, is unlikely to prevent violent crime, and will further reduce our ambition in respect of tackling its underlying causes. The alternative, to make a commitment to tackle root causes, need have no implications for civil liberties; indeed ultimately, it's the only way to guarantee liberty from crime to every citizen.