Interview: Dr Stephen O’Brien pioneers genome ‘bible’ for scientists to cure diseases

18 Sep 2013

US native and molecular biologist Stephen O'Brien (PhD in genetics), who is now living in Russia

The world-renowned geneticist, molecular biologist and conservationist Prof Stephen O’Brien is in Dublin this week to talk about animal conservation and genetic sequencing. He and a global group of scientist colleagues are assembling a type of ‘bible’ called Genome 10k, so the next generation of scientists can use technology to sequence genomes faster, and one day hopefully develop cures for degenerative diseases such as Alzheimer’s, multiple sclerosis (MS) and potentially cancer.

This evening, O’Brien is giving a public lecture at the Royal Irish Academy (RIA) on Dawson Street, Dublin 2. The lecture is part of an event series organised by UCD Earth Institute. It’s all about using genetics to conserve endangered species, and one day come up with cures for diseases.

A scientific career

O’Brien, who is chief scientific officer at the Theodosius Dobzhansky Center for Genome Bioinformatics in St Petersburg State University in Russia, flew into Dublin on Sunday night. He popped into the offices of to share part of his story of a scientific career that has spanned more than four decades.

One of the reasons that O’Brien is in Ireland this week is because he is a global colleague of the Irish scientist Prof Emma Teeling, the renowned bat expert.

The bat mobile

A professor at University College Dublin (UCD), Teeling is also the director of the Centre for Irish Bat Research.

Teeling had studied under the direction of O’Brien for many years at National Institutes of Health while she was a post-doc fellow. That was before she returned to Dublin, along with her husband, the astrophysicist Prof Peter Gallagher (he lectures at Trinity College Dublin), to take up a professorship at her old alma mater, UCD.

PhD from Cornell University – 1971

In global research circles, O’Brien is known for being a pivotal, game-changing molecular biologist and conservationist.

He earned his PhD in genetics from Cornell University in the US in 1971. He then joined the National Cancer Institute, National Institutes of Health as a post-doctoral researcher in that same year. And from there, as his research morphed, O’Brien eventually served as founder and chief of the Laboratory of Genomic Diversity from 1986 to 2011.

Prompted by the economic crash in 2008, which resulted in scientific budgets being slashed, and not just in the US, O’Brien seemed to want a new challenge.

At the National Institutes of Health, which is based outside of Washington, he had been co-ordinating the work of more than 160 scientists. But when the opportunity arose to head to St Petersburg post, he appeared to relish the opportunity to apply his scientific acumen to help nurture the scientific community in Russia, and beyond.

So, O’Brien moved there with his wife Diane in 2011.

In his role as chief scientific officer of the Theodosius Dobzhansky Center for Genome Bioinformatics in St Petersburg, O’Brien has been working with his team there to put together more than 62,000 animal and 424,000 human tissue/DNA specimens.

The latter area of his expertise is what O’Brien will be covering this evening at the RIA lecture in Dublin City.

Scientist with a social vision: to empower the next generation of biologists

O’Brien has been harnessing his tools as a molecular biologist to turn his attention towards conservation, specifically endangered species. Why? He wants to help pave the way for scientists around the planet to understand why diseases such as AIDS and cancer come about, and how the fusion of technology with science can one day help researchers come up with cures for such potentially devastating diseases.

That’s why he is now devoting himself to Genome 10k.

The whole idea, according to O’Brien, is that this will be a type of bible in the labs of all geneticists and scientists who are working to come up with cures for diseases ranging from diabetes to cerebral palsy and cystic fibrosis.


He kicked off his conversation on Monday by homing in on mammals. And of course bats were the order of the day.

It seems that one-quarter of all mammals are bats. There are 1,000 species of bats and us mere humans come down in the pecking order, depending on what way you look at it.

“There’s only 4,000 species of mammal of which human beings are one. Cats are another. Dogs are a third … orangutans, elephants.”

“We [human beings] are the most influential in the planet today, that’s for sure.”

That’s not to mention extinct mammals, also known as vertebrates. Think the dinosaur age, for instance.

And mammals all tie in with genetics and genome sequencing.

Communicating science: the digital age

Last year, the geneticist Dr J. Craig Venter gave a lecture in Dublin as part of the Euroscience Nano Forum on genetic sequencing and the digital age, and O’Brien wants to carry on the conversation this week.

He says the digital age, or the technology era, has empowered scientists to do genome sequencing faster, and thus come up for cures for life-threatening diseases faster.

“We started the Genome 10k project a few years ago. The benefits of having a whole genome sequencing have always been enormous, especially in model systems such as mice and rats.

“We realised that the technology for DNA sequencing has advanced so much that the Human Genome Project [2001] that originally cost in the order of US$2bn-US$3bn could be done today for a cost of under US$1,000.”

When the price began dropping, O’Brien got together with a few of his friends. Together, they decided that they could really start sequencing “virtually any genomes they could catch”.

“We realised that we needed to co-ordinate the biological community in order to get proper samples and to build ‘interest groups’ to participate in the characterisation of the genome sequences of, say, a fruit bat or a elephants or a gibben.”

A gibben, for instance is a lesser ape, according to O’Brien.

“The gibben is related to the great ape but is closer to humans in the evolutionary sense than are old-world monkeys or new-world monkeys such as owl monkeys or baboons.”

So, O’Brien and his friends knew they could genetically sequence virtually any of these species, but first they needed to get the biological scientific community on-board.

What is Genome 10k all about?

Genome 10k involves a consortia of scientists.

“We got together. I said to the scientists at a few meetings ‘what would you be willing to pay if we could sequence your favourite species? Would you be willing to pay for it?’,” he explained on Monday.

The idea then would be that colleagues of the scientists in question at a particular institute would write up research papers once such specimens that had been sequenced were validated.

“There was a lot of discussion. This was the original discussion in Santa Cruz in California in 2009. We invited not the brightest genome scientists I know, but we invited people who had spent their careers collecting specimens.” In other words, zoologists.

‘They had been filling up heir freezers with kidneys and livers and blood samples from bats and fish and mice.”

At the meeting in Santa Cruz, California, O’Brien asked these zoologists to sit down at their computers, there and then.

“I asked them to look up how many specimens represented how many species of vertebrate they could come up with if we were ready to sequence them.”

The idea was to start a database so that scientists could dip into a verified system to pursue and help carry on their specific research strands in the area of genetics.

And when he says vertebrates, O’Brien means five species: mammals, birds, reptiles, amphibians and fish.

“There’s about 60,000 species of vertebrates that have been named. So, for a round figure, we set a target of sequencing around 10,000 of these within the next 10 years.”

Giving back to society through IT and science

By that, O’Brien says he means giving a “genome script” to scientists. This would be a type of source code for making all of these species available to the “students of biology for the next generation”.

This is where O’Brien references the bible. He harks back to when the printing press was created. And it meant that the first book was printed was the bible. This was before it spawned the area of print publishing and the arrival of books to communicate everything from poetry, to voyages, to music, to art and science.

So, leaping forward to the 21st century …

“With the Human Genome Sequencing Project in 2001 that was the bible for scientists. Now, what Genome 10k is about is producing a ‘library’, to provide a gift for students. It will be an annotated genome script.”

Looking to the past to understand the future

And, by understanding the past, and what made animals that traversed the planet as far back as 100m years ago, even before the meteorite that struck Mexico 63m years ago, the idea is to help our scientists of the future spanning the globe understand evolutionary development, why some mammals don’t get cancer (think pelicans). The ultimate goal, it would appear, is to enable scientists make a difference to medicine.

The Black Death

GIF depicting the Black Death pandemic that swept across Europe in the 14th century, wiping out between 75m and 200m people. Scientist are not fully sure, but the bacterium responsible for the Black Death may have originated in China or central Asia, and reached the continent of Europe potentially via Oriental rat flies that abided on rats who were often voyagers on merchants ships from East to West. The Black Death, or the ‘Great Plague’ peaked in Europe between the c.1346-53. It also recourred many times, hitting places in Europe up until the 19th century. In all it is believed that the Black Death may have been responsible for the deaths of up to 60pc of Europe’s population

Coming full circle: the age of knowledge, age of technology, to the age of science and human capital

O’Brien finished off with the following analogy. Think of the ‘Black Death’ that swept across parts of Europe in the 14th century. Back then there was no medical surveillance or way of researching on a broad scale the pandemic and sharing the fruits of this research with other scientists.

Then in 1982 the start of the HIV epidemic in a few people in US cities of LA, San Francisco and New York baffled scientists as to what it was.

Flash forward to the technological era. In 2002 scientists were able to identify the Corona virus within three months.

And, in 2013, he says it can take scientists a day to understand what is causing a particular virus, and hopefully come up with drugs to resist such a virus

“It’s not about how much we know. It’s about how much we don’t know.” IT, he says has become the enabler for the problems that medicine has not solved such as degenerative diseases like MS.

And the real answer, believes O’Brien, lies in nature and watching how other mammals such as sharks live and survive diseases without any medical intervention.

Carmel Doyle was a long-time reporter with Silicon Republic