Genomics - Hope or hype?

Kat - We're joined by science writer Nell Barrie, and the story we wanted to talk about this month was about the publication of the HeLa genome. Now, these are cancer cells that were taken from a black woman in the 1950s I think, who had a very aggressive cervical cancer and they were basically the first cell line to be grown in the lab. And now, they've just gone all over the world. That's like more volume of these cells than the poor woman who ever existed in the first place. But there's a lot of controversy around the publishing of her genome. What do you think?

Nell - Well, I think it's a really interesting story and I think probably the first time most people heard of Henrietta Lacks with the book that was published recently, looking at the history of her life, what happened to those cells after she died and how essentially, she and her family were never involved or asked for their consent in any of the research that went on. I think people were quite surprised when the genome was published because it quickly turned out that once again, they hadn't asked her family for the consent to publish this genetic data. I mean obviously, I think most people would realise now that there's some quite interesting implications there because they're publishing her entire genome which obviously, her family share quite a lot of. So the question is, whose data is this, should they have asked them, and how do we resolve these kinds of issues in the future, I guess.

Kat - This is one of the themes that was coming out of the Genetic Society Spring Meeting is that it's not just your genome. You got a bit from your mum and dad, and you're passing it onto your children as well, and even your more distant relatives down the line will share some of your genes. So, I think the idea that - could you piece together what these, what her children or her grandchildren are like from her genome is an interesting question. And some people say, "No, you can't. It's all been messed up. You can't tell." But then other people have actually done a little bit of analysis and you kind of can.

Nell - Yeah, exactly and I think there was a quite interesting point made about when we're thinking about consent for these things. For example, when you've got things like organ donation, a person can consent to organ donation and then in some situations, that can be overturned by their family because they may not be happy about that after the person has died for example. Could that be the case with this type of information? You might consent and say, "I'm happy for my genetic data to be used" but then, as you were saying, essentially it's not just your data. So, who else needs to have consent? Who else needs to be consulted? What's really coming out of this is the fact that we've got all these data, we've got all this amazing sequencing technology now, we can do this so quickly, and the kind of law and the ethics just isn't keeping up with this.

Kat - I mean, policy takes years and years to thrash out and we're just cranking out genomes at a rate of knots. Now, it was the European Molecular Biology Laboratory EMBL that published this sequence and then quietly took it down after there was quite a few complaints about it, but with regard to the question of consent and whether this was ever consented for which it wasn't consented to publish it. Back when her cells were taken, they were taken from discarded tissue from when she was operated on and there was no kind of consent back then. So legally, the researchers don't have to do this. I think they are now working with the family to try and work out how to go forward.

Nell - Yeah, it's the kind of the way they expressed it is that it's this weird kind of limbo area. So, nobody is suggesting that the researchers broke any rules at this point, but it's more about what is ethically right, what should the kind of moral standpoint be, and I suppose, it's just interesting to think about how people might get involved in this type of research in the future because what's clear is that people are really willing to take part and help and to contribute tissue to clinical trials for example, and for that to be used later on in studies. But then it's really about how you can consent and the issue about informed consent, and do you really understand what that data is going to be used for. And the researchers who are taking samples right now, they may have no idea about the potential ways that could be used say, 10 years down the line if it's been stored in a freezer or something. So, it's really this kind of evolving field and I think the fact that we haven't got kind of international laws around these things makes it really, really difficult.

Kat - Yeah, that's an area that really needs to get sorted out. And also, the fact that it isn't just your consent. It's your family too, but how do we try and sort this out without hindering research and hindering research in the future, and without invading people's privacy in a way they might not want to is really challenging issue. But yeah, thanks for mulling that over with me, cheers!

Nell - Thanks!

Kat - That's Nell Barrie, science writer.

Scientists in Switzerland are the first to show that the two different types of fat in mammals - brown and white fat - can be converted from one to the other, challenging current understanding of fat cell fate. So far this research has been done using mice, but in the future it might lead to potential anti-obesity treatments.

White fat is the blobby stuff under our skin and around our organs. These fat cells get filled up with fatty droplets in good times and emptied when we need extra energy. In contrast, brown fat is only found in certain places in the body - although there's a relatively large amount in newborn babies - and burn fat and sugar to help maintain body temperature. Switching white cells into brown ones could be a handy way to lose weight by burning off extra calories, but until now this wasn't thought to be possible.

Writing in the journal Nature Cell Biology, the scientists focused on so-called 'brite' fat cells, which are brown-type cells that form within white fat in response to cold temperatures. Using special cell-tracing techniques, they discovered that these cells are generated by white fat cells switching fate as it gets chilly, rather than being generated by specific brown fat precursor cells. And not only did white fat switch into brown when it gets cold, they can switch back when the temperature warms up.

The researchers are now trying to track down exactly how this works, so they can design drugs that might push fat cells from white to brown and help burn up more calories. Sadly, this isn't going to help humans lose weight any time soon, but it's an important step on the road to understanding how different types of fat are formed, and how they might be manipulated.

Kat:: While it's useful to track down the gene faults responsible for rare genetic diseases, what patients and families really want are cures. And although individual rare diseases are by definition rare, added together they affect a significant proportion of the population. But while many scientific papers over the years have loudly proclaimed that finding a particular gene will "lead to new therapies", the reality is that progress in turning genetic data into treatments has been slow. I spoke to Professor Kate Bushby from Newcastle University, to find out how close we are to making this a reality.

Kate - I think that the disease I particularly work on Duchenne muscular dystrophy, forms a very, very good and saultary example of where we're going in that direction. Because the gene for Duchenne, the dystrophin gene, was identified in about 1986 and here we are in 2013 with maybe a couple of therapies about to get conditional approval, but we don't have disease transforming therapies on the cards for patients at the moment. And I think that's because we haven't really taken enough notice of the very long pathway that it takes to get new developments in genetics through the animal models into the trials and into the patients. And we haven't seen the drugs getting into clinic so far because of the time that that takes to assemble the patients, to train sites to the trials, to understand what the outcome measures are. And these are the barriers to translation research in rare diseases which we probably haven't addressed this dramatically enough as yet in order to truly benefit in the advances in genetics.

Kat - What are some of the key players in this who really need to get their act together to make a difference to patients with rare diseases?

Kate - So, key to all of these are the patients' organisations because with rare disease research in particular, they frequently provide the impetus for a group of doctors or a group of researchers to start working on a particular disease. They often provide seed funding for that and they also often contribute at a very great level to the development of patient registry. So you need your patient organisations on board. You need the researchers who make their initial discoveries and who, perhaps make these grandiose statements about how genetic discoveries are going to turn into therapies, to really get their head around what that means. We don't educate our scientists enough about the translational pathway I think so the basic scientists are a little naïve when it comes to understanding what the pathway is for the majority of them. And then the doctors, the people who see the patients need to understand the importance of directing them towards registries, whereby they can get linked into research. They need to become involved in developing natural history studies which will allow us to understand outcomes better and if possible, they need to get their resources in their own centre to get the trials up running as well. So, it's a partnership. All of these things are very much partnerships and we need to collaborate in order to make it work.

Kat - And I guess one of the big challenges is the money, and the money to develop drugs, the cost of drugs, and then just the money to fund the research. Where is that coming from?

Kate - Well, rare disease research has been getting some investment recently. The International Rare Disease Research Consortium known as IRDRC has brought together funders in rare diseases with the ambitious aims of having 200 new therapies for rare diseases by 2020 and diagnoses for all rare diseases by that date. So, there's a new emphasis on rare disease research which leads of course always to a little bit more money. The European Union has funded research in rare diseases at quite a high level and continues to do so, and that's a great priority of them. National funders have other priorities of course, but it's beginning to creep onto the agenda, and pharma is the newcomer on the block. Pharma is beginning to really make a difference to funding of therapy development in rare diseases, adding to the previous landscape where small patient organisations are often struggling to try and make progress. We now have a much broader range of funding opportunities available in this area.

Kat - And with the explosion that we've got in gene sequencing and understanding the genetics involved in the diseases, do you hope it will be faster than what it's taken for the research in Duchenne to get to the clinic?

Kate - It should be faster. We have new tools at our disposal. We've learned a lot. The worry is that what we learn in the Duchenne field isn't extended to other areas. So, other people have to start from scratch and sharing of information through meetings such as this and through other mechanisms for the collaboration are really, really important. And I think that's beginning to happen across the rare disease community because every new discovery shouldn't have to reinvent the wheel in terms of the processes by which they bring drugs to development. And there's a lot that people have learned so we should share that.

Kat - That was Professor Kate Bushby from Newcastle University.