More questions than answers

Some people like to go to church on Sundays, presumably to ponder some of the universe’s Big Questions. I do not go to church, and instead I’m spending the afternoon being distracted from what I’m supposed to be doing by some of life’s Small Questions.

Why has it hailed twice today? It’s June! It’s not even cold!

Will my figs survive? They surely didn’t evolve in a very hailstormy kinda place.

Why do I like thunder storms so much? Why aren’t there more of them in Vancouver?

Why is it called an o-ring? To distinguish it from other ring shapes? Is there an x-ring? A k-ring?

Why do North Americans say “I could care less”? In the UK we say “I couldn’t care less. I care the very minimum that it is possible to care”. You guys are effectively saying “I care slightly more than the minimum. I could be a little more emphatic with my apathy if I really tried”.

Why did I have so much caffeine today? That wasn’t smart.

When will I finish reading the latest paper I found to summarise on this blog? Presumably when someone helps me answer the questions above and I can start concentrating again. Or when the caffeine wears off.

Maybe I’ll just go and watch the Simpsons.

Will the movie be any good do you think?

Posted in English language, personal, silliness, Vancouver | 1 Comment

Reasons Not to Believe – Part 2

I am not alone!

Paul Gardner has also had a couple of papers misrepresented by Reasons to Believe.

Posted in bad people, creationism, Reasons not to believe in lies, science | 4 Comments

Endogenous retroviruses and the evidence for evolution

Here is my description of the part of my research that has been misrepresented by the Reasons to Believe website. See this post for an explanation.

My paper concerns the regulation of a human gene by DNA derived from an endogenous retrovirus (ERV). An ERV is a viral sequence that has become part of the infected animal’s genome. Upon entering a cell, a retrovirus copies its RNA genome into DNA, and inserts the DNA copy into one of the host cell’s chromosomes. Different retroviruses target different species and types of host cells; the retrovirus only becomes endogenous if it inserts into a cell whose chromosomes will be inherited by the next generation, i.e. an ovum or sperm cell. The offspring of the infected individual will have a copy of the ERV in the same place in the same chromosome in every single one of their cells.

This happens more often than you might think; 8% of the modern human genome is derived from ERVs. Repeated sequences of this kind were formerly considered to be non-functional, or “junk” DNA. However, we’re gradually finding more and more examples of viral sequences that appear to have some kind of function in human cells. For example, many ERV sequences play a role in human gene regulation. ERVs contain viral genes, and also sequences – known as promoters – that dictate when those genes should be switched on. When an ERV inserts into the host’s chromosome, its promoter can start to interfere with the regulation of any nearby human genes. In the example that I researched, the ERV promoter has become responsible for most of the expression of a particular human gene in the large intestine.

Creationists and intelligent design advocates like to think that because some ERVs have useful functions in the human genome, they must have been deliberately put there by a creator / designer with that particular purpose in mind. Of course, no-one can explicitly prove that that is incorrect – it’s not a falsifiable hypothesis, and therefore it’s not science. What we can show is that ERVs provide evidence in support of the theory of evolution.

Let’s imagine how ERVs would behave within a model of evolution by common descent. An ancient creature, let’s call it the common ancestor of all modern mammals, is infected by a retrovirus that becomes endogenous. All of the animal’s descendants (i.e. all mammals) would be expected to carry the same ERV insertion (ERV1) in the same chromosomal location.

Fast forward in evolutionary time. Different lineages have evolved and diverged from the original common ancestor and there are now many different types of mammal in existence, all carrying ERV1. A small rodent, let’s call it the common ancestor of mice and rats, is again infected by a species-specific retrovirus that becomes endogenous. This is ERV2. In a parallel event in a different lineage, the common ancestor of all great apes acquires a third insertion, ERV3.

Moving forward again, a fourth ERV appears in some of these new-fangled human thingies that are running around in Africa, but not in their hairier relatives who will eventually evolve into modern chimpanzees. The early humans spread out, and a fifth and (don’t worry) final ERV arises in a population that is isolated in a discrete geographical location. The infection does not spread to other human populations.

So what would we expect? Humans, chimps, mice and rats should all possess ERV1. The mouse and rat genomes will also contain ERV2, the virus that infected their common ancestor, but not the primate-specific ERV3, 4 or 5 insertions. All great apes will share an identical ERV3 insertion; all humans will also possess an ERV4 insertion that is not found in chimps or other apes. In addition, some, but not all, humans will carry an insertion of ERV5. The rodent-specific ERV2 insertion will not be found in any primate species.

Now that several genomes have been sequenced, we have begun to test these predictions. The patterns of ERV insertions observed in modern species exactly match the predictions made by the model described above. Some insertions are shared between humans and mice and represent truly ancient viral infections. Others are found only in primates, and not in other species, obviously derived from an infection of the ancestral primate species after its divergence from other lineages. More modern insertions are found only in humans, while the youngest ERVs of all are found in some humans, but not in all. We do not find any examples of ERV insertions shared by, say, humans and mice, but not by chimps. Insertions are always shared by all species, and only by those species, that have a common ancestor. ERV insertions therefore provide excellent support for the theory of evolution by common descent.

My particular favourite ERV is found in various primate species, and therefore must be at least 25 – 30 million years old. I compared the sequences and activities of the same ERV promoter in the human, chimp, gorilla, and baboon genomes. Despite some minor “single-letter” point mutations caused by DNA copying errors, the promoter had essentially the same function in all four species. I struggle to understand why any kind of designer would decide to use different codes to perform the same function in different species, but there it is. I hypothesised that the ERV was only allowed to persist (that is, its meddling in gene regulation didn’t kill the first organism in which it inserted, which was therefore able to pass the insertion on to its offspring) because the incoming ERV promoter behaved in a very similar way to the original host cell’s gene promoter. I wasn’t able to do the experiments I wanted in order to investigate this point, but another group subsequently did, and their findings supported my hypothesis. That’s what happens when you make and test falsifiable predictions.

I could go on and on about the role of ERVs in genome evolution, but this post is too long already. I would encourage anyone who’s interested to search for “endogenous retrovirus” AND evolution in the PubMed database of peer-reviewed research papers. You won’t find much in there about creationism or intelligent design. ERVs are also the subject of their own blog, a decent novel (although the sequel was disappointing) and a post on This Week in Evolution!

Posted in evolution, original research, science, virology | 31 Comments

Reasons Not to Believe – Part 1

I had an interesting email a few years ago from a collaborator who had recently co-authored the first paper to come out of my postdoctoral research. He had Googled himself, and our paper had cropped up in some unexpected places. As well as apparently being proof that retroviruses from space are reprogramming our genome, our research had also been co-opted by Reasons to Believe (RTB), a group calling themselves “the Premiere Science-Faith Think Tank” who claim to provide “Powerful New Reasons from Science to Believe in Christ”. My precious paper, the culmination of more than a year of hard work, was part of number 7 on their list of the “Top 10 Scientific Discoveries of 2003 that Support RTB’s Testable Creation Model”.

I have to admit that my first reaction was amusement. As a new British immigrant to Canada, I felt very secure in a secular society and dismissed creationism and intelligent design as primarily American problems. Look at these idiots, thinking that my paper supports their crackpot theories! I got on with my work and didn’t let the crazy website people bother me.

Over the last year or so, I’ve become much more aware of what some people call the culture wars in the United States. Science is under attack, and this is no longer an American problem. Creation “museums” exist in Canada and the UK, prominent European politicians support creationism, and a group called Truth in Science is threatening science education throughout the UK.

I eventually decided to reclaim my research from the people who have consistently tried to distort the science to support their own agenda. I checked a few months ago and found my paper in the RTB archives. I emailed the website’s creators, explained that they had misunderstood the meaning of my paper, that it actually provided evidence in support of evolution, and politely asked if they could please remove it from their site. I repeated my request a couple of times. I never received more than a bland message in reply saying that they would look into it.

Now here’s the thing – my wonderful former room mate decided to shut down the email account that he’d set up for me without giving me a hint of warning. So I lost all my correspondence with RTB, and never heard from them again. It’s possible that they tried to contact me and had their message bounce back (although if they’d really wanted to reach me, they could have found me through the contact information within the paper in question). All I know is that my paper’s still on their website, and I want it removed.

So here is my public statement: my research that is cited on the RTB website actually supports evolution (the details are in a separate post due to length. I got a bit carried away).

I plan to send this link to the RTB website, explain what happened with my email account, and ask them to respond. I’ll post any correspondence here. I will also start to contact other authors whose work is cited in the RTB archives and try to solicit some similar statements refuting the use of their work to support creationism. If anyone reading this has also had a paper misused by RTB or any similar group, please let me know and I’ll be in touch.

If you have a website of your own, a link to this post would be much appreciated – it would be great if Google searches for RTB would bring up statements like this one somewhere near the top!

Don’t believe in lies and misinformation!

Posted in bad people, creationism, rants, Reasons not to believe in lies, science | 6 Comments

Vulcans! In Vancouver!

Sorry, couldn’t resist. I don’t have access to The Lancet – does anyone have a subscription? Were there photos in the original paper?

_____________________________________________

Update: no photos. How disappointing. Thanks anyway Factician for sending the paper!

Posted in freakishness, medicine, Vancouver | Comments Off on Vulcans! In Vancouver!

Why I got out of research

My last post explained how I got into research. This post concerns why I got out*.

I loved many aspects of bench research. I think that performing original research is a privilege that few people are lucky enough to experience. It is almost a cliché among scientists, but there’s really nothing like the feeling when you’re the first and only person in the world that knows this fresh piece of information about how the world works.

I also enjoyed the sense of freedom. There are not many careers in the world that grant such independence so early on. I had my own projects, my own schedule. If I didn’t put the work in, it was only really my own prospects I would harm, which for me was a huge added incentive to get on with it and publish!

I loved attending conferences. It’s just not the same as an exhibitor. I loved presenting my work and getting instant feedback and new ideas. But my favourite part was the writing. I actually enjoyed writing my PhD thesis. Well, most of it anyway. And I was never happier than when writing a paper. There was something about writing up results than encouraged me to think about things in a different way, to clarify my ideas and develop new ones. I like to re-read my old papers every once in a while; as I’ve said before, I’m very proud to have contributed, even in a minor way, to my field.

So why did I get out? I came to realise during my PhD that a permanent research career might not be for me. First of all, I seemed to enjoy writing about my work more than I enjoyed actually doing it. I also wanted a life. To be successful in research, you have to give up a lot – weekends, evenings, friendships, sometimes relationships. I’d seen too many people sacrifice too much. I worked every weekend for the last year of my PhD and hated it. But then again, I knew that a few years of postdoctoral work would be great training for my ultimate goal of a science communications career. (The easy path to a temporary Canadian work permit** was another attraction…)

Money is another perennial problem in research. I could live on my low salary for a while, but there’s a reason why virtually no postdocs own their own homes. My fiancé, who’s a carpenter, was shocked when I told him how much I made; it was less than half of his average salary. All this and no job security beyond the standard 3 year contract.

Even if you do make it big and get your own lab, you’re suddenly responsible for your whole team’s job security as well as your own. Grants depend on the quality of the researcher and their work, yes, but also on trends, fads, luck, nepotism, reputation, political interference and geography. My own efforts to attract postdoctoral funding were thwarted in part because my standard British three year PhD just didn’t generate as many publications as the five to six year period of postgraduate work undertaken by my North American competitors. I managed to complete my contract using my supervisor’s core funding grant, but the pressure to attract funding is ridiculous at every level. I don’t know of any other career in which someone near the top can be highly respected by their peers, regularly invited to speak at international conferences, and still have to fight for their funding every few years. Grant renewal reviews are no fun for anyone, least of all the lab head.

So that’s why I’m here, gaining more useful experience to help me reach my ultimate goal of a career in science communication. That’s also the raison d’etre of this blog. (Feedback always welcome…)

Rant over. I will read, digest, summarise and communicate some more actual science soon. I promise.

*My apologies to former supervisors if you ever come across this. I enjoyed working for both of you, I really did. Ask my former colleagues if you don’t believe me!

**Postdoctoral research is one of something like three or four job categories that doesn’t require your employer to prove that there’s no-one already in the country who could do the same job, and that employing you would have a positive impact on the wider Canadian job market.

Posted in career, personal, rants, science | 10 Comments

Why I got into science

I don’t usually believe in fate, but I do believe that I was meant to be a scientist. Whether it’s innate curiosity and logic, or a mixture of other traits, I seem to be very well suited to biology in general and genetics in particular.

The various jobs I aspired to over the years changed as my understanding of science matured. I’ve noticed that young children always want to enter the professions they’re most familiar with. Most kids in my elementary school wanted to be a teacher, nurse, firefighter, train driver – jobs we were familiar with and understood. I decided early on that I wanted to be a vet, preferably in a zoo.

I grew up reading James Herriot’s books and watching All Creatures Great and Small on the BBC. It seemed like such a great job, spending time with all those cute and interesting animals. Then I spent some time volunteering at a vet’s surgery in my early teens, and realised that my career would be an endless procession of overweight cats and dogs getting their annual shots.

My next career aspiration again came via the BBC; I wanted to be David Attenborough. (yeah, OK, I still kinda do). I even entered a couple of competitions through the BBC Wildlife magazine, hoping to win the first prize of a day at Kew Gardens or the BBC Centre with my hero. If I couldn’t be David Attenborough, I wanted to be a field zoologist or marine biologist. Whales! Dolphins! Tigers! Orangs!

Greenpeace membership in hand, I paid extra attention during biology lessons. I was lucky enough to have a fantastic teacher who was a true inspiration to me. (If it wasn’t for her, I might have had to become an engineer instead). When I was about 14, she started to teach us about some monk in Central Europe who bred pea plants in the 19th century. I remember the lesson to this day. She told us what was understood about the nature of heredity at the time. She told us how Mendel designed his experiments and meticulously carried them out. She told us about the famous 3:1 and 9:3:3:1 ratios of different traits that he observed in first generation hybrids. Then she told us how the theory of discrete and independent allele inheritance with no blending was worked out, and showed us how to logically map out all possible allele combinations, according to that same theory, to arrive at a ratio of 3:1 or 9:3:3:1.

Well, I was hooked. It just made so much sense. Subsequent lessons were just as logical. Descent with modification, natural selection? Made sense. The modern synthesis, incorporating Darwinian theory and molecular biology? Yep, made so much sense, how could it be any other way? The more details I learned, the more everything fell into place. I once had a different biology teacher tell me that she felt she never had to teach me anything, that I always seemed to know it already. I explained that partway through every explanation she ever gave, some area of my brain would light up and complete the process before she finished speaking. Genetics was so logical, so elegant, so obvious once you started to think about it.

I went on to study genetics at university, where specific fields started to appeal more than others. I was particularly interested in molecular evolution; viral genetics; cell cycle control; and the transformation from normal to malignant cells. My PhD thesis combined a couple of these areas, focusing on the transformation of chicken fibroblasts by a growth-promoting gene carried by a virus. My data led me into the field of gene expression regulation.

My search for a postdoctoral position had two parameters. It had to involve gene expression regulation, but in an interesting, exotic kind of way. And it had to be in Vancouver, a city I had visited and fallen in love with. An early literature search brought up a paper that fit the bill perfectly, co-written by a graduate student who was later to become a colleague and friend. So a few months later, I was on a plane to Canada to study the evolution of transcriptional regulation by endogenous retroviruses. (More on these fascinating pieces of our genome will come later; anyone who’s interested in them right now should visit ERV’s blog).

I am immensely proud to have contributed, even in such a small way, to the field that has fascinated me ever since my high school lesson about Mendel’s pea plants. My papers are still cited, which brings me more pleasure than it decently should. A newly arrived postdoc in my former lab once told me that one of my papers was a fairly major factor in her decision to emigrate to Canada and join our group. The circle was complete.

As my profile says, I am still a scientist and always will be. However, I am no longer in research. The reasons for that will be the subject of my next post.

Posted in career, education, personal, science | 2 Comments

I’m a specialised generalist

Another month, another conference. This is June, so it must be clinical immunology in San Diego.

As a postdoctoral researcher I used to go to one major meeting per year, usually the American Society of Human Genetics. That was when I could justifiably consider myself to be an expert in my field, with a deep understanding of a narrow area. I got to give two oral presentations and got some great feedback on them. I could attend sessions where I understood the vast majority of what was being presented, and even ask an occasional question when I dared.

These days I go to lots of different conferences, and have a more superficial knowledge of a much broader area. I definitely feel less connected than I used to, a feeling epitomised at a recent dermatology meeting where the speaker obviously said something very controversial that elicited a collective gasp of astonishment from the audience. It went right over my head.

The advantage of my new broader scope is that I get to read about subjects that I just wouldn’t have had time for when I was immersed in my own speciality. I scan lots of journals’ tables of contents, read various abstracts, subscribe to New Scientist, and hang out on scientific blogs whenever I get the time. This means that when a friend starts to ask me about a scientific item they saw on the news, there’s a better chance that I can reply “oh yeah, I was reading about that last week”, rather than “ooh, sorry, that’s really not my field”.

I think I’d like to maintain most of the breadth of knowledge I’ve started to accumulate, but gain some more depth. I’m working on incorporating that goal into my current job, while this blog is part of my extra-curricular attempt to stay in touch with the latest original research.

I’m trying to be a generalised specialist.

Posted in career, conferences, science | 1 Comment

On the Origin of Tumours by Means of Natural Selection

I had an interesting conversation with a medical doctor this week. Granted, I’d much rather he’d chosen not to discuss cancer stem cells while removing a suspicious mole from my arm, but these things often seem to happen to me when a physician asks what I do for a living.

Our conversation got me thinking about how the development of cancer mirrors the process of evolution. This comparison first occurred to me during my undergraduate degree in genetics. To understand the molecular nature of cancer, we had to learn to see things from a tumour cell’s point of view.

Cell growth and division are usually very tightly regulated processes; various mechanisms have evolved to ensure that a cell can only divide into two daughter cells if the conditions are right. The correct growth factor chemicals must be present, DNA replication must have been successfully completed, the cell must have reached a certain minimum size, and be in an appropriate position with respect to other cells and tissues.

A tumour develops when these inhibitory mechanisms fail. DNA replication is not 100% accurate, and some daughter cells will receive mutations in genes that usually help to regulate cell division. Most mutant cells will be weeded out and marked for destruction when they fail to meet other cell division criteria, but the occasional gene mutation escapes notice and survives.

Imagine a mutant cell that no longer requires growth factors in order to grow and divide. The cell will divide regardless of its chemical environment, passing on its mutation to both daughter cells, each of which will then divide into two more mutated cells. In this way the mutation is passed down through successive generations of cells. If there are no growth factors present, the mutant cells will continue to divide while normal cells are inhibited. The mutant cells will rapidly come to outnumber the normal cell population. You might say that they have a selective advantage, and therefore produce more offspring.

Eventually, one of the rapidly dividing, growth-factor independent cells will acquire a second mutation in another inhibitory gene. Suddenly, we have a growth-factor independent cell that will divide when it reaches a smaller size than normal. This cell will be able to divide before its merely growth-factor independent relatives are ready. Again, this mutation confers a selective advantage, and subsequent daughter cells will outcompete and outnumber the original population of mutant cells. As cells grow and divide faster and faster, more DNA copying errors creep in. Some of these errors even increase the frequency of further mutations. The end result of this evolutionary process is a clonal population of aggressively growing cells that can move to other locations in the body to produce secondary tumours.

This process is obviously disastrous for the host. But you can not deny that the tumour cells themselves are immensely successful. Their ability to divide more rapidly than the body’s normal cells lets them produce more offspring, and increase the frequency of their beneficial mutations within the total cell population.

The gradual evolution from normal to malignant cells illustrates a very simple natural law. If an individual produces a number of offspring via an imperfect copying mechanism, the result will be a mixed population of individuals with slightly different characteristics. If one of the variants is able to produce offspring faster than its peers, then those offspring will be over-represented in subsequent generations. In this way, characteristics that increase reproductive success are inherited by more individuals and continue to increase in frequency, gradually changing the overall demographics of the population.

This really should be self-evident, and I have a very hard time understanding why evolution deniers find the concept so difficult to grasp. The gradual accumulation of mutations during cancer development is well documented, but I don’t think I’ve ever seen these data used to teach the principles of evolutionary theory. I fear that I would not make a very good teacher myself as I would become too easily frustrated with those who just can’t seem to get it. But if anyone reading this is involved in science education, please let me know what you think.

Oh, the suspicious mole turned out to be only slightly dodgy. No matter how cool evolution is, I’m happy to avoid observing the survival of the fittest within my own puny Celtic skin.

Posted in evolution, medicine, science | 2 Comments

Beach-front office, here I come!

I came across a very cool use of Google Maps via a comments thread on Pharyngula today. Flood Maps lets you see how rising sea levels are projected to alter the coastline around the world.

My house looks like it will be just fine, even with a 14m rise in the sea level. My office will be right on the beach, which will no doubt improve the quality of our monthly lunchtime BBQs. It’s lucky that life here will be so good, as I won’t be able to leave – the airport and most of the bridges will be gone.

The long climb up the hill on my daily cycle ride homewards suddenly seems so much more appealing. Now I just need to work on buying that boat.

Posted in Climate change, Vancouver | 2 Comments