Resurrection 2! Book Review: How to clone a mammoth Beth Shapiro Princeton University Press 2015

Extinct animals don’t have rights” Hoskins, Jurassic World 2015 –
A statement so richly embedded in politics and science that I let out such a long sigh in the cinema.

I suppose it is good timing for this book to be released a couple of months before Jurassic World came out. As I have mentioned before in a previous blog post Resurrection! Bringing extinct species back from the dead, we are not going to be seeing dinosaurs being bought back. But since I wrote that blog post in 2014, there have been developments in the technology that could to some extent bring back extinct species.

One of those developments is the CRISPR-Cas9 method which I have written about in another blog post Humans Re-Designed, and which is going to dramatically change human therapeutics. It is with this technological feat in mind that Professor Beth Shapiro at the University of California, Santa Cruz who is also part of the Revive and Restore Project, writes this book How to clone a mammoth.

Shapiro takes us through a whirlwind adventure step by step that might lead to a cloned mammoth. While her book is written for the lay-person with little background in molecular biology, geneticists and those in the field of ancient DNA can still find some entertainment and humour in how she writes. She quite literally provides us with a story, narrating expeditions she has been on with appropriate cliff-hangers. So for instance, I skipped the few sections on DNA degradation (which admittedly I thought would have been more suitably provided in one place rather than in different sections and chapters), but I was left wondering at the end of chapter 4 just exactly who the men with guns were!

She also provides a theoretical thought experiment; that despite the challenges and numerous obstacles that we face in an attempt to clone a mammoth, with each step she always begins with the assumption that the previous has been successful. Her chapters are certainly presented in that way after a general introduction: Select a species, find a well-preserved specimen, create a clone, breed them back, reconstruct the genome, reconstruct part of the genome, now create a clone, make more of them, and set them free.

As easy as it may seem it is not! The truth is that there are so many obstacles and limitations that you actually start to wonder if it is at all possible to clone a mammoth. I found myself ironically laughing at yet another impossible task to overcome in chapter 8: Now create a clone. But as Shapiro writes, there are many teams around the world taking on one of these obstacles at a time and you do get to hear their stories as well, one of which includes coaxing wild Spanish ibex down from shelves (!)

My favourite chapter is the last: Should we? Perhaps more because as a scientist I find it incredibly funny and frustrating (in that order) at how science can be mis-interpreted and how the media can sensationalise. In reality, Shapiro does not present this science as the only solution to biodiversity/conservation issues. Even she worries that some might think this method is a quick-fix. She covers the contentious issues and ultimately presents de-extinction as a proposal that needs each obstacle examined in detail. She finishes off touching on policy issues that might affect such species.

I recommend this book to anyone with an interest in biodiversity and conservation matters. It crosses the divide between ancient DNA and ecology nicely. To answer the question: can mammoths be cloned? Shapiro answers: “No”. But there is a twist! And there is only one way to know what that twist is, and to do that you will need to read the book for yourselves.

http://www.amazon.co.uk/How-Clone-Mammoth-Science--Extinction/dp/0691157057/ref=sr_1_1?s=books&ie=UTF8&qid=1435235702&sr=1-1&keywords=how+to+clone+a+mammoth

Image taken from www.amazon.co.uk How to clone a mamoth

 

Kitty Science

Cats are everywhere on the internet providing the perfect procrastination technique and let’s face it, everyone has at least one friend who is crazy for cats. I have quite a few but one in particular wins the cat obsession prize. She would dress up as a cat for Halloween, wear anything cat related (preferably space cats), would yell out from the back of a lecture theatre on a talk about cats and dogs “YAY CATS” and entice two cats into her household with catnip. Her hen party was consequently cat themed.
To honour this obsession and all those feline fanatics, this blog article focuses on recent scientific cat news.

Brainwash Cat

From: http://www.omgcatsinspace.com/

 

 

 

 

 

 

 

From Wildcat (Felis silvestris lybica) to Domesticated Cat (Felis silvestris catus)

It turns out cats were not originally domesticated in Ancient Egypt. The first feline remains were from a Neolithic site in Cyprus dated to 9500 years ago unearthed by the archaeologist Jean-Dean Vigne from Paris in 2001. But cats are not native to Cyprus.
Carlos Driscoll from the National Cancer Institute, USA led a study examining wildcat DNA (from around the world) to determine where cats were first domesticated. He found that of the five distinct wildcat lineages: the European, South African, Central Asia, Chinese desert and the Near Eastern, it was the Near Eastern lineage that gave rise to domesticated cats. Interestingly, the study highlighted that domesticated cats are genetically closer to wildcats from the Israel desert, Bahrain, Saudi Arabia and (as my cat-obsessed friend would love if she knew) the UAE. It has thus been suggested that people from Turkey brought domesticated animals with them when they settled in Cyprus.

The first cat that had its full genome sequenced was in 2007. She was an Abyssinian cat called Cinnamon who lived at the University of Missouri, USA. The study published in Genome Research described the structure of the cat genome with an emphasis on genetic diseases, as cats have about 200 genetic diseases similar to humans including type 2 diabetes, asthma, leukaemia and the cat version of HIV; feline immunodeficiency virus. This was followed up by a study in 2014 which sequenced additional cat genomes and identified genes and traits selected for in domesticated cats. These included genes for fear conditioning, reward/stimulus behaviour, and within the past 200 years when cat fancy took off, aesthetic qualities such as hair colour, texture and pattern began to be selected for. Now a sequencing initiative led by Leslie Lyons at the University of Missouri aims to sequence 99 cats as part of the grand project 99 Lives to improve cat health care. They revealed their initial results at a meeting in San Diego, California in January. Anyone with a cat can participate if you can get your cat to remain still long enough to get a DNA sample!

I iz giving u present human

As much as cats may have become more docile since they have been domesticated, they are still highly temperamental creatures ready to pounce and kill any poor unsuspecting bird or animal, and then drag it into your kitchen, or worse place it conveniently on your pillow which you wake up to. But why do this? Researchers in Washington suggest that it could be because they are trying to teach you hunting skills. Female cats are more likely to bring back dead animals and it is in their nature to try and teach their litter to be effective predators. They will do this by bringing back small mammals at various stages between life and death to be mauled by the kittens as practise.
To capitalise on this, the animal charity in London Wood Green teamed up with the cleaning and DIY service Handy to provide kittens and cats at the rescue service to Londoners to get rid of mice. The idea has been welcomed as a way for kittens aged between 2-8 months to get used to new environments which they will eventually move into, dramatically reducing the cat’s stress on arrival.

Soft kitty, warm kitty, little ball of fur, happy kitty, sleepy kitty, purr, purr, purr

In a new environment, a cat will always get to know its surroundings and would like to feel in control of it before it can completely chill. Even the charity Wood Green suggests adding a piece of cloth with the scent of their old home into the new one just to make the cats feel relaxed. Cats do experience stress and it can affect their immune systems. Suffice to say, they certainly know how to de-stress… by taking refuge in boxes! Dr Claudia Vinke at the University of Utrecht, Netherlands conducted a study comparing stress levels between two groups of new feline arrivals at a shelter, and found that those who could take refuge were a lot less stressed. It is not just boxes though; it could be any container, just take a look at this video.

Faster, human, feed, feed!

As it turns out, cats have their own language when communicating with us as research by Sharon Crowell-Davies at University Georgia, USA revealed at a conference this year. It appears as though cats will try a certain vocalisation on us and if it gets the desired result, they will continue to use it (BBC Video). A cat’s meow is the perfect example of how they can so easily manipulate us. Dr Karen McComb at the University of Sussex investigated why we just can’t ignore a cat’s purr. The “cry” contains a low and a high frequency element to it. Remove the high frequency and this removes the urgency.

If that wasn’t enough to manipulate you, then perhaps you need to be infected by the uni-cellular parasite Toxoplasma gondii. When it infects rodents, it makes them fearless and more prone to take risks, like taking a stroll near a cat which will ultimately meets its doom by said cat. The parasite reproduces in the cat’s digestive system and continues to infect the cat in cycles. People can be infected by the parasite through kitty litter or contaminated water, but it can’t reproduce in us. In pregnant women, it can lead to miscarriage. If we are infected we will experience flu-like symptoms but once that passes we remain carriers for life, and it will rewire our brains. Interestingly it has different effects in men and women. It makes men more introverted, suspicious and rebellious, and it makes women more extraverted, trusting, obedient and friendly, something that the cat could benefit from. This certainly gives a new meaning to the term Crazy Cat Lady!

Now I don’t own a cat even though I remember my childhood cat that lived to the grand old age of 19. I am not obsessed with them but I can see the allure of the cute kitty (I had a cat-fling just last year with my neighbour’s cat Theo before he disappeared in November). Despite the science revealing why the little critters will always bring dead animals into our homes or how they actively manipulate us, these fur balls on four legs will always be dear to our hearts, and even if you don’t have one, well there are always YouTube videos.

This blog piece is dedicated to Karima Steele 16 May 1983- 3 February 2015. She is the friend who wins the cat obsession prize. She was doing her PhD at the Neuroscience department, University of Sheffield. Her memorial service was held on 9 May 2015 at the Sacred Heart Church, Hillsborough.

Karima with Cat

Karima Steele with her cat Kira courtesy of Suzan Ahmad

Humans Re-designed

Usually those who write about genome editing or designer babies tend to start off by describing a dystopian world probably referencing Gattaca, where if you were conceived naturally you are a “God-child” labelled an invalid and deemed lower class.
The topic of designer babies has been explored before in a Science Brainwaves blog post: Designer babies- What’s It All About? but a recent technological breakthrough brings this topic back with a vengeance. In this blog post I explore the reality behind it.

1975 Asilomar, California
Recombinant DNA technology boosted biotechnology and its potential drastically, so in 1975 a meeting was held to discuss the relevant safety issues. The result was an agreement of principles and recommendations to be applied to the research. A similar meeting was held this year- 24 January in Napa, California and some of the same people that attended the 1975 meeting also attended this one. Their goal was similar to the one in 1975: to discuss principles, review safety and ethical guidelines on the new technology that had developed in the interim.

The Technology
The technology that had developed in that time was the application of zinc finger nucleases (ZFN) (Urnov et al 2010 Nature Reviews Genetics 11, 636–646) and CRISPR-Cas9 (Jinek et al 2012 Science 337: 816-821) for genomic engineering. Both act like a pair of scissors, cutting DNA and allowing for an insert.

ZFN have zinc finger protein (ZFP) sites that bind to targeted DNA while the enzyme nuclease (in FoKI) cuts the DNA. The first time this was used as a tool for genetic engineering was to knockout a gene in a Chinese hamster ovary cell. However there were issues involved in its design, synthesis and validation that posed a barrier to its adoption. Sangamo BioSciences a biotech company in California took on this technology to further develop it. But CRISPR-Cas9 seems to have superseded ZFN.

Urnov Edited

Urnov et al 2010 Nature Reviews Genetics 11, 636–646

 

 

 

 

 

 

 

CRISPR-Cas9 is a molecular system that gives bacteria adaptive immunity to viruses. It comprises of a protein that guides RNA to bind to DNA and then breaks the DNA. Even though CRISPR has been known to cut target DNA since 2010, it was not until 2011 when Cas9 was included and in 2012 it was adapted with the protein to break DNA. The Cas9 that was previously included was that of the bacteria Streptococcus pyogenes, however in a paper published just this month in Nature a smaller and more efficient Cas9 has been identified allowing for a broader range of genetic targeting.

Doudna and Charpentier

Doudna and Charpentier 2014 Science 346: 1077

 

 

 

 

 

 

 

 

Setting the scene
The technological developments are coming thick and fast. Big players are emerging (some at MIT and Harvard in Boston, USA and China) and fertility companies are starting to commercialise work conducted by stem-cell experts. The reason for this is that there is big difference in the type of cells that can be genetically engineered. Germline cells are sperm and ovaries which once edited can pass on changes to the next generation. Somatic cells are all other types which only affect the individual to whom they belong. The scientists have issue on both technical and ethical grounds with editing germline cells and its effect on future generations. The idea behind genome editing is to correct genetic diseases, such as cystic fibrosis, haemophilia, some cancers and sickle cell anaemia. While everyone agrees on the medical benefits, editing germline cells carries a different and significant impact affecting . . . take a breath, here is a long list by Nuffield Bioethics Council: justice, sustainability, crop breeding, livestock engineering, pharmaceutical development, individual liberty, autonomy and human reproduction.

From the meeting in January the scientists came to a unanimous agreement: All genetic germline modification must halt. They identified recommendations and outlined the next steps on ensuring safety and open discussion. Sending in their recommendations to Science, this was consequently picked up on by Nature and The Guardian. The dust had not even settled completely when just last week Junjiu Hang at University of Guangzhou in China published in Protein and Cell that he had genetically modified embryos, even though they would not give rise to live births. Despite this both Nature and Science rejected his paper on ethical grounds and this has caused a ripple effect of additional worry within the scientific community. On the other side, some scientists are worried that the media or others might demonise this work to such an extent that the full benefits might never be realised. Not everyone in the scientific community agrees with this moratorium.

So what now? Even the Chinese scientists agree that using CRISPR-Cas9 clinically is premature. With the red light bringing the studies to a (potential) halt, the debate is entering the political arena. For now you will not be seeing any re-designed humans, but this is not over so watch this controversial space!

A Child’s Curiosity

“What is gravity?” asks my then four year old nephew to his family.
Quite an inspirational question from a four year old! But then again, at the time they were all watching the highly acclaimed Cosmos; the science documentary hosted by Neil deGrasse Tyson. A child’s curiosity clearly knows no bounds when it comes to the world around them, and I am astounded by the equally captivating questions his brother asks me (“What does e in math[s] mean?”)
It is sad that in later years children eventually lose their interest in science. In 2008, The Telegraph published a report with statistics that showed some children were losing their interest between primary and secondary school (42% of 9 year olds were interested in science, but this drops to 38% of 12 year olds and 35% of 14 year olds). In 2013 Ofsted reported an assessment of science education and recommendations based on a survey [Maintaining curiosity: a survey into science education in schools] conducted between 2010 -2013. CaSE in London responded positively to this report and has called for the UK Government to heed these recommendations.

I had the chance to observe such inspirational curiosity during my Easter holidays when I visited my cousin and her children (hereafter referred to as my niece and nephews) in Boston, centre of scientific excellence. It really doesn’t get any better than that! One of the things I was particularly looking forward to was extracting DNA from strawberries with them. I had of course previously done this with Science Brainwaves at a school outreach event in 2011. Just telling my 11 year old niece and 9 year old nephew about this got them really excited. When I told them their dining table needed to be cleaned, my nephew (who prefers to kick a football around the house much to his parents’ disapproval) was so eager that he could not clean the table fast enough! I complemented this little experiment with a brief 101 on DNA and PCR (polymerase chain reaction, which copies DNA). When I interviewed them later about it, they told me they loved it and would gladly do it again. Score 1 for science! If doing practical experiments benefits children so much, then it certainly makes the removal of practical work for A’ Level exams by Ofqual in the UK dubious. Naturally, this move has been criticised and on the 12th May 2014, a hearing was hosted by the Commons Select Committee to discuss this proposal.

I also had the opportunity to visit some of the scientific attractions of Boston with the kids; the New England Aquarium and the Museum of Science. I found that the trip to the aquarium was definitely worthwhile. My nephew had his own epiphany linking the ecology of sharks and their prey to the food web, as he dictated later in the evening. I was amazed and a little scared when I had the chance to touch stingrays and a baby shark in the giant ‘touch-tank’. But I wasn’t the only one in seventh heaven. It was interesting to find out that my niece actually wants to be marine biologist. Score 2 for science. I asked my 9 year old nephew what he wanted to do and he replied with a list of potential careers: archaeologist, cosmologist or footballer. I was completely honest with him when I said that he might make more money becoming a footballer, there probably won’t be very much opportunities in archaeology, but that cosmology might be more fulfilling. He didn’t seem too upset or waylaid by this. I neglected to ask the youngest, as at the time he was 4 years old and most of his ambitions included chocolate and tickling. I will ask him another time.

When it comes to their parents encouraging them into science, my cousin and her husband do not hold back! Amazed by my nephew’s questions, the family is now subscribed to the Scientific American and together they all sit down to watch Cosmos. This documentary, playing on Fox and National Geographic, follows on from the Carl Sagan version which played in 1980. I watched the second [Some of the Things That Molecules Do] and fourth [A Sky Full of Ghosts] episodes, glad that the second episode provided a neat and tidy introduction to genetics and evolution, the ideal precursor to extracting DNA from strawberries. I was really astounded at how the show pitched itself perfectly to both adults and children. The parents and all three kids were glued to the screen, and I found the balance between explanation and visuals in complete harmony. But of course, a documentary like this does not go unnoticed by the Creationists in the USA, especially when evolution is involved. In an article in the Huffington Post, the show was criticised by Creationists for not given its due time on Creationism. I asked my niece and nephew what they thought and they make the same claims as any scientist would make: Why give inaccurate information to the public, especially when there is evidence to back up what we already know? Score 3 for science.

For the final flourish in this scientific journey with my niece and nephew I tell them I write a monthly blog for Science Brainwaves. So I asked them to read Resurrection! Bringing species back from the dead, and get their thoughts and feedback. They both would like to see the sabre tooth cat brought back (clearly indicating they have not seen Jurassic Park). My niece is for bringing back species from the dead as she thinks it will make great study material. My nephew on the other hand is a lot more cautious. I don’t think I can score this as either for or against science, but I’m definitely happy to see this younger generation at least considering the ethical options. Either way, the final score is 3 for science, I’m still the Cool Fun Aunt and now I can happily watch and nurture their scientific ambitions to reality.

 

DNA Extraction

Doing DNA extraction with my niece and nephew

NEAQ

The touch tank at the New England Aquarium

 

Interbreeding humans: The Sassy Palaeolithic Action

Are you confused about the different types of humans that got it on with each other?
If you are, then in this blog entry, I provide a summary factsheet style of the pairs of hominids that interbred with each other, with evidence for and against it, and the current conclusion. All dates are expressed as years before present, and be aware that in the field of ancient DNA, human contamination is always an issue that can potentially confound the results.

Hominid Action Pair #1:     Neanderthals     +        Humans: Non-Africans
Home-turf:                            Europe/Asia                         Global
Lived from:                        400,000 – 30,000             200,000- present
When and where:                     47,000-65,000 Middle East
Evidence for getting it on: FORinterbreedingIf the different colours represent different genetic make-up, then the answer to the question “Where did the modern humans get their genes from?” can only be “from mating with Neanderthals”.

Evidence against getting it on: AGAINSTintebreedingThis model clearly produces the same pattern but without mating.

Current status: The literature arguing against interbreeding has been focused on the pitfalls of the method used. Nevertheless, new methods are now confirming that Neanderthals and humans were up in a tree K.I.S.S.I.N.G. Now, we are starting to identify what genes we got from them.

 

Hominid Action Pair #2:         Denisovans      +      Humans: Asians/ Oceanians
Home-turf:                           Siberia (Tropics?)                       Oceania
Lived from:                            ? – ~50,000                       200,000- present
When and where:                      S.E Asia and prior to 44,000
Evidence for getting it on: It’s the same case as the evidence for mating between Neanderthals and humans, except here the genes that went into the ancestral populations of the Aboriginal Australians, Near Oceanians, Polynesians, Fijians, East Indonesians, and Philippine Mamanwas and Manobos can only have come from the Denisovans.
Evidence against getting it on: While models are presented in the literature for discussion, they have been argued against. The consequence of which is that the results are described as a best fit to the data.
Current Status: We know that the action took place BUT we don’t know enough about the Denisovans. We only have a tooth and small finger bone from a Siberian cave. Watch this space!

 

Hominid Action Pair #3:              Denisovans       +         Homo erectus?
Home-turf:                              Siberia (Tropics?)        Africa, China, Indonesia
Lived from:                                 ? – ~50,000               1.9 million years- 150,000
When and where:                                         ? and Asia?
Evidence for getting it on: The Denisovan tooth has some features that you can find in some of the older Homo species, and the DNA appears to also look quite archaic. Homo erectus was widespread across Asia, so it does seem likely that the two hominids crossed paths.
Evidence against getting it on: At the minute, there isn’t any. This model was proposed as the most likely scenario to a result that arose from another study.
Current Status: As already said before, we don’t know that much about the Denisovans. There are still a lot of gaps making this a hypothesis.

 

Hominid Action Pair #4:             Neanderthals        +       Denisovans
Home-turf:                                    Europe/Asia              Siberia (Tropics?)
Lived from:                                400,000 – 30,000              ? – ~50,000
When and where:                                    ? and Europe/Asia?
Evidence for getting it on: NeintoDeEvidence against getting it on: Not presented.
Current Status: This has just recently been published, and the amount of DNA material from the Neanderthals into the Denisovans is calculated to have been very small. More analyses will have to be done.

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Summary
Here is a final tree summarising the relationships between the hominids, and the arrows indicate where interbreeding took place. Adapted from Prufer et al 2014.

SummaryWhile I used a lot of literature to create the above summary, if you are looking for more information then I recommend Veeramah and Hammer 2014, Nature Reviews Genetics 15, 149-162 as it provides an up to date informative review while also including relevant references.

Resurrection! Bringing extinct species back from the dead

My best friend has nightmares about dinosaurs; T. rexes chasing and searching for her as she hides behind furniture. I don’t blame her. Courtesy of Jurassic Park, I’m sure there are plenty of others who have had similar nightmares. During my PhD, I once had a nightmare that Neanderthals were back and trying to take over Europe. But is it really possible to bring back species from the dead?

At first glance, it seems to be more difficult than the movies give credit for. In 2009, the New Scientist published an article outlining the method for any Dr Moreau wannabes, but also why the technology is not available for it to work:   

1- Obtain a complete and accurate genome

2- Package and assemble this genome into chromosomes

3- Identify a suitable surrogate to provide the egg and to gestate the embryo to full term

But as technology is moving at a face pace the limits of scientific accomplishments are being further tested. Revive and Restore is a project aiming to push the boundaries for resurrecting extinct species. Inspiration for this project came when the last passenger pigeon (a species hunted to extinction for its meat) named Martha died in Cincinnati Zoo in 1914. Several species have since been chosen as candidates to be resurrected, including a range of birds, the quagga, the Easter Island palm and several Pleistocene mammals. The first meeting held on the 8 February 2012 brought together conservation biologists and geneticists to assess the feasibility of resurrection. Since then the project has established a list of criteria to examine the suitability of each candidate species, e.g. how will bringing back the species answer scientific questions, is it possible to re-wild a species and, if selecting a species further back in time, is there enough preserved DNA. Sure enough in 2013 an article What If Extinction Is Not Forever? appeared in Science discussing the risks versus the benefits. The objections fell into five categories: animal welfare, health, environment, political and moral, and the benefits included: scientific knowledge, technological advancement, environmental benefits, justice and the “cool” aspect of it.

One of the reasons why the passenger pigeon was selected is because there are plenty of samples that are young enough to obtain good quality DNA. The key issue therefore lies in the survivability of ancient DNA sequences. The potential rests firstly in obtaining increasingly older DNA sequences and secondly, ensuring that the genome is of high quality. The oldest DNA sequence obtained to date is the 700,000 year old horse genome from Canada, a far cry from what was once an hypothesised maximum of 100,000 years old (Shapiro and Hofreiter, 2014). Sequencing technologies have also drastically increased genome coverage (how many times a gene is “read” a bit like each time you re-read a book you pick up on more information and with better accuracy). The Denisovan genome, for instance, before the use of the new sequencing technology enabled a coverage of 1.9 fold, which increased dramatically to 30 fold once the new techniques were applied. Nevertheless even with the new technology to analyse fragmented DNA, Shapiro and Hofreiter (2014, p. 1236573-2) state “it may not be possible to sequence any eukaryotic palaeogenome truly to completion”- a sad case indeed for the 11 year old boy who once asked me at a Science Brainwaves workshop “can we bring monsters back?” Assuming he meant dinosaurs and without getting into the logistics with him, I gave him the theoretical but not entirely true response of ‘yes’. He then exclaimed “COOL” really loudly and wondered off. To be honest, I didn’t really want to break his heart, and I may just have inspired him to become a scientist! A similar question was posed (in a considerably much more professional manner) at the Royal Society meeting in London Ancient DNA: the first three decades in November 2013. Towards the end of the talk The Future of aDNA by Professor Michael Hofreiter, a colleague from UCL asked “can we reconstitute from ancient DNA (putting aside the technical details) a viable sequence to create a viable organism?” The answer was a resounding no. When it came to resurrecting dinosaurs, Professor Hofreiter quite clearly stated that the field of ancient DNA will never be able to go that far back in time. With an added flourish came the phrase “don’t waste your time or money!”

So should we be worried about dinosaurs chasing us, or Neanderthals taking over? With the advancement of technology opening up the possibility of resurrection, it is only those that have not been extinct for very long that could be resurrected, such as the dodo or the passenger pigeon. The debate on this however continues: It is through this approach that together scientists, policy-makers and the public can work together to ensure that this new science is used in a mature and sensible way. As for my best friend, she is relieved and hasn’t had a dinosaur nightmare since.

Jurassic Park, copyright IMDB Universal Pictures 2012

Jurassic Park, copyright IMDB Universal Pictures 2012

Neolithic Revolution in the air!

THE NEOLITHIC REVOLUTION WAS A KEY MOMENT IN THE PREHISTORY OF HUMANS. It sparked civilisation as we know it- settlements were established, crops were grown and animals were domesticated transforming the economy of subsistence globally. Beginning in the Levant (Near East) around 12,000 years ago, the Neolithic Revolution spread into Europe 8000 years ago and lasted up until 4000 years ago when the Bronze Age began.

The major question is how did this revolution spread? Did the indigenous hunter gatherers adopt farming solely though cultural transmission? Or did the farmers pass on their practices alongside their genes? These two models (see diagram) – culturally diffused model (CDM) and demic diffused model (DDM) – originally seen as two polar opposites as mechanisms of the spread, have been debated throughout the 20th century. By identifying the proportion of Mesolithic/ hunter-gatherer and Neolithic/ farmer genes within the current gene pool (see diagram), the correct model could be identified.

Classical genetic markers in present day populations (such as blood groups) appear to lend support to the DDM revealing a genetic cline from the Near East towards the West. But modern genetic markers can reflect population processes that have taken place both before and after the Neolithic spread. Instead ancient DNA (aDNA) provides a unique window of opportunity to look back into the past. Ancient DNA studies do come fraught with difficulties. Over time DNA degrades and fragments into short molecules. Usually this means any contaminating modern DNA is favourably extracted and analysed instead. Nevertheless strict and rigorous protocols exist to minimise contamination and new technology has been optimised for aDNA extraction.

The archaeological record has shown that as farmers migrated across Europe, two different routes were taken as indicated by distinct ceramic styles. One route was through Central Europe, from Hungary to Slovakia, Ukraine and through to Paris, as shown by the Linearbandkeramik (LBK) and Alföldi Vonaldiszes Kerámia (AVK) pottery styles. The other route represented with Impressed Ware/Cardial culture was along the Mediterranean coast. aDNA studies have been conducted on samples from these different sites and cultures, and the picture that emerges is one more complex than just picking one model over the other. It certainly appears that the two routes have their own model: while the Central Europe/ LBK route shows little to no genetic continuity between the Mesolithic hunter-gatherers and the Neolithic farmers, the Mediterranean route tends towards genetic continuity and therefore a level of gene flow between the two populations, a pattern which even seems to lead up into Sweden.

But this most certainly is not the end of the story. For one thing, the genetic studies carried out were analysing the mitochondrial DNA (mtDNA), which is inherited solely down the female line (men inherit their mothers’ mitochondrial DNA but will not pass it on). In one study, it was found that of Spainish Neolithic samples while the mtDNA belonged to hunter gatherer groups from the Palaeolithic, the Y chromosome was shown to be from the Neolithic Near East. This does seem to suggest that the role of men and women during the advance of the Neolithic differed to some extent. Additionally, it also appears that the change to farming practices did not happen as rapidly as expected, and was not as clear cut. In two recent papers (with a particular focus on Germany), it was found that hunter gatherers and farmers lived alongside each other for about 2000 years and, interestingly while the Mesolithic hunter gatherers and the Neolithic farmers had their own distinctive gene pools, at some point in the Neolithic there were intermediary groups with shared ancestry and lifestyle undoubtedly reflecting the transition that was taking place.

There is a level of difficulty when studying the past; we cannot always state processes or cause and effects with a perfect degree of certainty, but we can say what the evidence appears to suggest, and in this case it appears to suggest a high a degree of complexity as the Neolithic Revolution took hold. There is never just any one specific model that can answer our questions, and there will always be other lines of evidence to explore. To answer the original question how the Neolithic Revolution spread cannot be placated with just one simple answer. It is never that easy. But as aDNA analyses show, we can still get one step closer to that very complicated answer.

More information:

Bollongino et al 2013 Science 342 (6157) 479-481

Brandt et al 2013 Science 342 (6155) 257-261

Gamba et al 2011 Molecular Ecology 21 (1) 45-56

Haak et al 2005 Science 310 (5750) 1016-1018

Lacan et al 2011 PNAS 108 (45) 18255–18259

Pinhasi et al 2012 Trends in Genetics 28 (10) 496-505

Skoglund et al 2012 Science 336 (6080) 466-469Neolithic Revolution

 

 

 

Reproduction Revamp: Stick Insects and Going It Alone.

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Timema cristinae: making a lack of a love life cool.

Love can be tough. If you wish awkward dates and trawling through match.com were a thing of the past, you could take a leaf out of this stick insect’s book. Tanja Schwander (University of Lausanne) studies how Timema stick insects are changing the dating game. Rather than reproducing with a partner, female Timema have developed the ability to produce offspring individually.  There could be a number of causes for this bizarre transition from sexual to non-sexual offspring production, so read on for a how-to guide in ditching dating.

Conversion to non-sexual reproduction may occur genetically. When female Timema are prevented from mating, some eggs that haven’t been fertilised by sperm hatch and develop. Could this virgin birth scenario, reminiscent of biblical times, replace sexual reproduction in Timema? Or are virgin births merely a strategy to ensure female stick insects can carry on their line when opportunities to mate are thin on the ground?

Alternatively, a type of bacterial infection may stimulate non-sexual reproduction. Infecting bacteria are only transmitted through the female sex cell, the egg, and so males slow the spread of the bacteria. In light of this, the bacteria devised a cunning strategy to eliminate males: inducing a kind of non-sexual reproduction that produces only female offspring. Could bacterial infection be the instigator of non-sexual reproduction?

Schwander’s studies of genetic data reveal the virgin birth scenario cannot explain the change in Timema reproduction. Conversion to non-sexual reproduction may occur genetically, but not via virgin births. To determine if bacterial infection causes the stick insect’s lack of libido, Schwander cured the infection. This restored sexual reproduction and production of male offspring, proving bacterial infection can result in non-sexual reproduction. Watch this space; could Boots’ next bestseller be bacteria to eliminate human males?

Designer Babies- What’s It All About?

Throughout the social and scientific worlds, there is controversy surrounding the potential to genetically modify embryos to create ‘designer babies’. These are embryos that have been screened for genetic diseases, and will therefore only contain selected desired qualities chosen by the parents. However, there are many stories in the media which exaggerate and distort the facts- and this can even be seen in the term ‘designer babies’ itself. It is important to think about the likelihood and implications of this idea, plus to outline what actually gave rise to this concept.

We could suggest that the idea of genetically engineered embryos or the ideas that led to this originated in 1978 and the first in-vitro fertilisation (IVF) treatment. The procedure gave and still gives hundreds of infertile couples a chance to have a child by transferring an egg fertilised in a laboratory into the mothers uterus. It subsequently led to a procedure known as preimplantation genetic diagnosis (PGD). This is a technique used on embryos to profile their genome- it is a form of genetic profiling and embryo screening and is a more technical and accurate way of regarding ‘designer babies’. In terms of health benefits, using PGD means embryos can be screened outside the womb. Embryos can be selected that only carry normal and healthy genes, and are therefore free from genetic abnormalities. Whilst this technique is currently popular, PGD could in the future be used to select any desired specified trait of a child, such as eye colour, intelligence, and athleticism; be used to select embryos to be without a genetic disorder, to increase successful pregnancies, to match a sibling in order to be a donor, for sex selection and therefore be used to design your own baby. Selecting the gender of a child is already possible due to the fact only the X or Y chromosome needs to be identified, but other traits are more difficult due to the amount of genetic material required. Recent breakthroughs have meant that every single chromosome in an embryo can be scanned for genes involved in anything from Down’s Syndrome to lactose intolerance using a single microchip, but how advanced is this and what are the ethics behind this?

There are a large array of ethical, social and scientific concerns over the concept of creating a ‘perfect’ child. Some people worry that in the future there will be an imbalance between genders in the general population especially in societies that favor boys over girls, such as China. Also, a key issue suggested is that there is an element of eugenics to this idea- PGD will mean that people with ‘unattractive’ qualities will be lessened and potentially society may discriminate against those who have not been treated. If we look at this from a more extreme perspective, it could be suggested that we may end up with a race of ‘super-humans’ and a divide between those who have been treated and those who haven’t.  Also, this selection of genotypes suggests a potential deleterious effect on the human gene pool, meaning less genetic variation. Whilst at first this may seem positive due to the fact you could eliminate genetic disorders such as hemophilia A before it becomes prevalent in the body, it is also likely that new diseases may evolve and accidentally be introduced into the human race. Due to the decreased gene pool, only partial evolution would be able to occur and therefore we will be more susceptible to new diseases having a dramatic effect. It is clear from this evidence that regulations must be put in place and strictly enforced before any new advances are made.

So, how close are we to being able to ‘customise’ our children?
In terms of altering genes already present in the embryo, we are already well on our way to refining this technology. Scientists have been altering animal genes for years, and germline therapy is already being used on animals. Germline gene therapy is now being closely linked and developed with PGD- and it could soon be used to change human genetics. Our germline cells are our sex cells (egg and sperm), and using this branch of gene therapy essentially involves manipulating and adding new genes to the cells. The clear possibility from this in terms of PGD is that any trait can be added to an embryo to create a designer baby. This may involve adding a gene to stop a genetic disorder being expressed in a baby’s phenotype by fixing them as they are noticed in PGD, but it could also mean that only certain people will be able to advance in society.

On he other hand however, before these ‘more advanced’ humans are created we need to learn more about the genetic code. The basis of all genetic technologies lies in the human genome, and whilst PGD advances are ever-increasing, at present we can only use this technique to look at one or two genes at a time. Therefore, we cannot use it to alter the genes in embryos, and this would logically lead us to think about gene therapy, but the current lack of technology and the strict regulations regarding experimenting with germline gene therapy makes it unlikely that anyone will be able to create a completely designer baby in the near future.

Designing our babies is a reality that government bodies and various organizations are beginning to accept and address fully, and society’s view of the moral implications behind PGD and gene therapy being a key factor in determining how far this concept can advance; there will be increasingly new debates and controversy over the acceptable applications of gene technologies in humans and human embryos.

 

 

 

 

 

Biotech for all – taking science back to it’s roots?

This morning I came across a very interesting TED talk by Ellen Jorgensen entitled “Biohacking — you can do it, too” (http://on.ted.com/gaqM). The basic premise is to make biotech accessible to all, by setting up community labs, where anyone can learn to genetically engineer an organism, or sequence a genome. This might seem like a very risky venture from an ethical point of view, but actually she makes a good argument for the project being at least as ethically sound than your average lab. With the worldwide community of ‘biohackers’ having agreed not only to abide by all local laws and regulations, but drawing up its own code of ethics.

So what potential does this movement have as a whole? One thing it’s unlikely to lead to is bioterrorism, an idea that the media like to infer when they report on the project. The biohacker labs don’t have access to pathogens, and it’s very difficult to make a harmless microbe into a malicious one without access to at least the protein coding DNA of a pathogen. Unfortunately, the example she gives of what biohacking *has* done is rather frivolous, with a story of how a German man identified the dog that had been fouling in his street by DNA testing. However, she does give other examples of how the labs could be used, from discovering your ancestry to creating a yeast biosensor. This rings of another biotech project called iGem (igem.org), where teams of undergraduate students work over the summer to create some sort of functional biotech (sensors are a popular option) from a list of ‘biological parts’.

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The Cambridge 2010 iGem team made a range of colours of bioluminescent (glowing!) E.coli as part of their project.

My view is that Jorgensen’s biohacker project might actually have some potential to do great things. Professional scientists in the present day do important work, but are often limited by bureaucracy and funding issues – making it very difficult to do science for the sake of science. Every grant proposal has to have a clear benefit for humanity, or in the private sector for the company’s wallet, which isn’t really how science works. The scientists of times gone by were often rich and curious people, who made discoveries by tinkering and questioning the world around them, and even if they did have a particular aim in mind they weren’t constricted to that by the agendas of companies and funding bodies. Biohacking seems to bring the best of both worlds, a space with safety regulations and a moral code that allows anyone to do science for whatever off-the-wall or seemingly inconsequential project that takes their fancy – taking science back to the age of freedom and curiosity.