Why not ask a scientist?

One of the most infuriating habits of the media is its tendency to allow unqualified showmen to discuss scientific matters of which they know next to nothing.

This is particularly noticeable in the United States, where politicians and news presenters regularly make claims about climate science and evolutionary biology that demonstrate their own paucity of understanding concerning these subjects. Why don’t news channels invite scientists working in relevant fields onto their shows, rather than political and television celebrities that are simply not qualified to pass judgment on scientific matters, and who regularly get their facts wrong and contribute to misinforming the public and promoting scientific illiteracy?

To pick on people like Bill ‘tides go in, tides go out’ O’Reilly and Glenn ‘global warming sceptic and intelligent design advocate’ Beck for distorting scientific accuracy would almost be too easy, and the problem is not just limited to the American Right. Bill Maher, a Left-of-centre comedian and talk show host in the United States that I otherwise quite like, has made some shockingly misinformed and ignorant statements about vaccines.

Similarly, Intelligent Design advocate and scientific fraud William Dembski was invited on to the Daily Show with John Stewart to “debate” the “question” of evolution. And who was on the “other side” of this supposed debate – a geneticist? A palaeontologist? An evolutionary developmental biologist? No, it was a historian, Professor Edward Larson. Now, I have nothing against Prof Larson, and I know he has written on the historical development of evolutionary theory. But surely it would have been judicious for at least one member of the panel to actually be a practising life scientist?

In my experience, scientists are often very eager to discuss their research, and by in large do a pretty good job of explaining it in an engaging way for the general public, especially if helped along by a decent science journalist. And even if radio and television companies want ‘celebrities’ for their shows, there are plenty of scientists that have written popular books aimed at a general readership, and some have even achieved semi-celebrity status. How about Richard Dawkins, P.Z. Myers, Sean B. Carroll, Adam Rutherford, Steve Jones or Eugenie Scott? Hey, if they wanted a Christian to explain evolutionary science they could have asked Kenneth Miller or Francis Collins.

Instead, the Daily Show hosted an intelligent design advocate (well known for misrepresenting scientific data and concepts), a historian, and a ‘new age mystic’ named Ellie Crystal, who I can only describe as bizarre (she babbled about “sacred geometry”, or something. I didn’t really get it.) The show producers could have invited a philosopher that actually knows something about evolutionary biology in her place, like Barbara Forrest, Daniel Dennett or Michael Ruse.

So why don’t they ask the experts?

I suspect this is due to a combination of perceived mistrust in science and scientific authority, a worry that science is “boring”, simple apathy and intellectual laziness, and, in the case of Fox News at least, a desire to wilfully warp scientific evidence to fit around predetermined political ideology (particularly regarding ‘sociologically controversial’ subjects like evolutionary biology, climatology, and embryonic stem cell research.)

And the effect really isn’t harmless. Denying anthropogenic global warming at a time when millions of people living in coastal areas are facing the reality of rising sea levels; denying evolution when the extensive use of antibiotics is causing the emergence of multi-drug resistant, highly virulent pathogens such as recalcitrant TB; denying the efficacy of vaccines when many debilitating diseases, such as measles, mumps, rubella, diphtheria, polio and (recently) cervical cancer can be easily prevented with their use, and many more (HIV, malaria, schistosomiasis) still await the development of efficacious life-saving vaccines; blocking funding into embryonic stem cell research, which has the potential to benefit millions of people who suffer from incurable degenerative diseases like Parkinson’s; and interfering with the creation of highly nutritious genetically modified plants that can alleviate the world’s global food crisis, saving millions from starvation; are all major threats to the prosperity of human beings and non-human animals around the world. (Michael Spencer’s ‘Denialism: How Irrational Thinking Hinders Scientific Progress, Harms the Planet, and Threatens Our Lives’ makes for superb reading on this subject.)

And beyond the global threat to human civilisation, scientific illiteracy in the media can adopt more personal forms of cynicism and nastiness.

My motivation for writing this little rant came after hearing extreme right-wing radio host and bigot, Rush Limbaugh, accuse Michael J. Fox of ‘faking’ his Parkinsonian symptoms in order to gain a sympathy vote for the Democrats. Referring to a video Fox released promoting stem cell research, Limbaugh said that Fox had either adopted the shaking movements as an affectation, or deliberately missed taking his medication to accentuate the symptoms. Limbaugh described Fox as “really shameless.”

It takes serious chutzpah to accuse someone suffering from intractable neurodegeneration of lying about their condition; presumably Limbaugh consulted a neurologist, neuroscientist, psychiatrist or other healthcare professional before making this accusation? Unfortunately not; had he done so, he would have been informed that Fox’s jerky movements are known as dyskinesia, and this is a classic sign of Parkinson medication. (Parkinson’s Disease itself causes severe rigidity and muscle stiffness, slow movements and tremor. Ironically, far from missing his medication, the large jerky movements of the head and arms apparent in Fox’s video occur as a side-effect of medication used to combat Parkinson’s Disease.)

Had I been in Fox’s position, I’d have been tempted to release a three-word statement that simply read, “Fuck you, Limbaugh”. But evidently Fox is a bigger man than I. His response was measured and laudable, and included the following piece of insight:

We all have a right to speak up and say what we think is right, and we all have a right to fight for the things that we believe in, and I believe that science should move forward in this country. Science is a big part of the American story, and we need to start writing a new chapter.

Here here. If only more people in the media would listen to that message, and allow the voice of reason and science to rise up above the background buzz of ignorance and ill-informed, misinforming opinion.

Sensational Science from 2011

Happy Near Year! That’s 2011 over.

Unfortunately, Charlie Brooker’s amusing review of the year neglected to mention any of the fantastic science that has been published over the last twelve months (a tragic omission!)

The most significant breathrough of the year, as selected by the journal Science, was the discovery that sexual transmission of HIV is dramatically reduced if infected individuals receive antiretroviral therapy. The study, conducted by the HIV Prevention Trials Network (HPTN), found that transmission through heterosexual sex from an infected partner to a previously uninfected partner was reduced by 96%, if the infected partner stuck to their antiretroviral drug regime. In the study’s own words,

“… we found that early antiretroviral therapy had a clinical benefit for both HIV-1–infected persons and their uninfected sexual partners. These results support the use of antiretroviral treatment as a part of a public health strategy to reduce the spread of HIV-1 infection.”

This may sound rather obvious, but it had never been formally confirmed that antiretrovirals protect against transmission of the virus to new hosts, in addition to offering direct benefit to the affected person. As the editors of Science said while justifying their choice of discovery,

 

“Because of… profound implications for the future response to the AIDS epidemic, Science has chosen it as its Breakthrough of the Year.”

Science‘s video on the breakthrough rundown is also worth a watch.

Two of the journal’s nine runners-up include the discovery that ancient, extinct species of human, such as the famous Neandertals, interbred with modern human populations after we migrated out of Africa a few tens of thousands of years ago (which I have written about before), and the elucidation of the structure of Photosystem II, which is an integral component of photosynthesis in plants and microbes. I regard the latter discovery as potentially one of the most far-reaching, because there’s a small but significant chance it may ultimately help save the world. Let me explain.

Photosystem II includes a protein structure known as the Oxygen Evolving Complex (OEC), which splits water molecules (H₂O) into Hydrogen ions (H⁺) and free oxygen (O₂). Plants use the elecrons released from this reaction to turn carbion dioxide into sugars. By solving the structure of the OEC at incredible resolution, we may be able to design our own version of the protein and thus split water into hydrogen and oxygen ourselves, using the power of the sun. The chemical reaction between hydrogen and oxygen in turn could be harnessed to generate electricity (the so-called hydrogen economy).  And the best part is, the only waste product is… water. No more carbon footprint, no more anthropogenic global warming, no more nuclear waste. That is why I think solving the structure of Photosystem II, particularly in atomic resolution at the OEC, deserves its place as one of the great discoveries of 2011.

Another runner-up was the early publication of some preliminary data from the Stage 3 Clinical Trial of the RTS,S malaria vaccine. To be honest I thought this article got a lot of hype for not much substance. The results are, as yet, incomplete; the overall vaccine efficacy only came out as 34.8% and the follow-up wasn’t long enough to see how long protection will last. Some other promising malaria vaccine research from 2011 included the live vaccine published in Science,  and the vaccine candidate called Basigin, which seems essential to parasite invasion of red blood cells. These seem like worthier runners-up to me (although I do declare some conflict of interest, as the lead author on the Basigin paper is my supervisor…)

So as not to neglect the technology/ physical science side of things, I think the development of a high-speed camera at the Massachusetts Institute of Technology that captures one trillion frames per second has to rank as a top breakthrough of the year. The camera is so fast it can film beams of light actually moving through space at the speed of light! In the future, the technology may be used for medical imaging in an analagous way to ultrasound, but rather than bouncing sound waves off of tissues, as with ultrasound, it would be light itself that bounced off surfaces to be detected by the astonishing camera. The exact way in which the light scattered could then be used to reconstruct the object’s surface in unprecedented detail.

As for where things are headed in 2012, the areas I am most excited about are whole-genome DNA sequence studies and the work coming out of the Large Hadron Collider (will we finally find the Higgs Boson? And what about that faster-than-light Neutrino?!) Breathroughs in renewable energies would be nice too, along with a cure for ageing. Culturally, I’d love to see a rise in the number of scientific publications from Arab nations following this year’s Arab Spring, especially among female scientists in those countries. We can but dream, I suppose.

One thing I would bet my house on is that (pending a catastrophic natural disaster) there will be a whole host of fascinating new findings revealed in 2012 that I can choose between to write about in twelve months time. I can’t wait.

What does an elephant, an Iberian mole and a Giant Panda have in common?

Answer: they have all independently evolved bony anatomical structures that function as fingers (or thumbs) that are not derived from tetrapod pentadactyl digits.

So I don’t think I’ll be head hunted by Marks & Spencer for Christmas cracker jokes any time soon, but it is true nonetheless.

The typical body plan of a four-legged land animal (known technically as a tetrapod) consists of four limbs, each limb with an upper bone (in the case of a human arm this is the humerus), two lower bones (the radius and ulna), a group of smaller bones (our wrists) and a variable number of digits, each consisting of several thin cylindrical bones, known collectively as the polydactyl limb.

In our case, the upper limbs have become arms, with four fingers and one opposable thumb (thus we are pentadactyl). The upper limb of bats has become adapted for flight, with elongated ‘fingers’ supporting membranous wings. Some animals have lost digits over evolutionary time, such as hoofed mammals like horses, while others have lost limbs altogether, as in the hind-limbs of Cetaceans (whales and dolphins), or all four limbs in snakes. But all these creatures are still unmistakably related to other tetrapods with more ‘typical’ body layouts.

The Giant Panda (Ailuropoda melanoleuca) possesses the standard pentadactyl limb, with five ‘fingers’ comprising each paw. But it also has a sixth digit in the two front paws that work functionally like opposable thumbs, allowing the panda to grip bamboo shoots more effectively.

This ‘pseudo-thumb’ is not the result of duplicating an extra finger during embryological development. In fact, it is formed by elongating one of the bones found in the panda’s wrist known as a sesamoid bone.

Sesamoid bones are embedded in tendons, and are essentially hardened calcifications of the tendon itself. The largest sesamoid bone in the human body is the patella, which lies suspended in the kneecap between the quadriceps tendon above and the patellar tendon below.

One of the sesamoid bones suspended in tendons around the panda’s wrist has been lengthened over evolutionary time, and supported by additional muscles and nerves, to form its pseudo-thumb. Steven J. Gould wrote about this in his collection of essays, The Pandas Thumb, noting it as a perfect example of what he called an exaptation – the usurping of a piece of anatomy that evolved for one reason into a completely different role to exploit a new environment. It is a great demonstration of the blind opportunism of natural selection; having a lengthened wrist bone for a thumb isn’t perfect ‘design’, but it is what was available and it works, and that’s all that matters.

Indeed, the improvised sesamoid thumb must be advantageous because another group of animals has evolved a very similar structure completely independently. Talpid moles, such as those you’d find in a local golf course, also have a sixth digit in their front paws that acts as a rudimentary thumb. But rather than assist with gripping bamboo, as in the panda, the mole’s ‘thumb’ probably evolved to help with digging. The exact developmental pathway for sesamoid bone elongation and thumb formation has been elucidated in one species of mole, Talpa occidentalis (the Iberian mole). It would be fascinating to learn whether pandas independently hit upon the same developmental pathway, or whether entirely novel developmental processes are at work producing similar results.

Writing this week in the journal Science, anatomists have uncovered a similar bone buried within elephant’s feet. A massive sesamoid is located in all four of the elephant’s foot plates (unlike the panda and mole, which only possess elongated sesamoids in their front limbs). While the five conventional digits in the elephant’s pentadactyl limb point forwards, the extra sesamoid points backwards into the dense heel pad, helping to support the animal’s massive weight. Revealingly, the extra bone only appears in the fossil record from around 40 million years ago, when elephants first started increasing in size.

Evolution does what it has to, and when five digits just aren’t enough, whether it’s for eating bamboo, digging holes or supporting ten tons of herbivorous body mass, natural selection can stumble across unexpected solutions repeatedly and independently, namely by making thumbs out of wrist tendons. As well as exaptation and opportunism, the sesamoid digits exemplify another evolutionary principle, that of Orgel’s Second Law: evolution is cleverer than you are.

Sayonara, Christopher Hitchens

Christopher Hitchens died aged 62 on 15^th December 2011 of pneumonia, secondary to oeseophageal cancer. His death is a huge loss to political commentary and journalism, to the pursuit of truth wherever it takes you, to wit and irony, to the spoken word and to all those who value freedom, open-minded enquiry and the principles of humanism and secularism.

Hitchens disavowed the term ‘hero’; mere primates always fall short of the pedestals others place them on. (This is one of many features of organised religion Hitchens detested, the “ridiculous fetishization” of fellow mammals such as Joseph Ratzinger or Jesus Christ). He certainly had his shortcomings, flaws and vices; Hitchens was no super-human nor ever claimed to be. But he was a fellow primate that I greatly admired, that inspired me, and that I will miss.

I first discovered Hitchens with his best-seller, God is Not Great; his barbed wit, breadth of knowledge and eloquent evisceration of religious arguments made for a highly entertaining read. From there, I read back as much Hitchens as I could get hold of, from his assessment of the war in Iraq to a history of blowjobs.

Through his writing, I learned of the United States’ involvement in the illegal overthrow of Salvador Allende in favour of the right-wing dictator, Augusto Pinochet, in Chile; of Henry Kissinger’s support for Indonesia’s invasion and destruction of East Timor; of the illegal bombing raids in Cambodia during the Vietnam War; of how Agnes Bojaxhiu (‘Mother Teresa’) took money from the Duvalier family that ruled Haiti as a dictatorship, and then spent it all on proselytizing hard-line Catholic conservatism; of Bill Clinton’s decision to bomb the Al-Shifa pharmaceutical factory in Sudan, which produced antimalarial drugs vital to poor people in the region, and whose destruction resulted in thousands of unnecessary deaths; of the Armenian Genocide following World War I, and of the hideous persecution of Kurdish people and Marsh Arabs in Iraq. For opening my eyes to these and so many other international events and movements, I owe much to Christopher Hitchens.

A master debater, Hitchens’ spoken eloquence was also put to devastating effect in debates with theologians such as Dinesh D’Souza, William Lane Craig, Alister McGrath, David Wolpe, John Lennox and Frank Turek. I know I am not alone in saying that watching these debates on YouTube helped formulate, refine and generally sharpen my own views on matters of religion and faith.

Towards the end of his life, while “living dyingly”, as he memorably phrased it, Hitchens wrote movingly on his experiences as a cancer patient. His Vanity Fair articles provide a fascinating window into “Tumourland”, and while at times humours, they certainly did not sugar-coat the grim reality that awaits us all:

… one finds that every passing day represents more and more relentlessly subtracted from less and less. In other words, the process both etiolates you and moves you nearer toward death. How could it be otherwise?

Nevertheless, the knowledge of his imminent demise seemed only to focus Hitchens’ mind. His somewhat irritating tendency to become visibly bored by his opponents during debates was lessened; indeed his writing and debating post-diagnosis was some of his finest (the debate with Tony Blair on whether ‘religion is a force for good in the world’ was superb). As Richard Dawkins wrote in his obituary, the bravery and integrity with which Hitchens faced his own mortality made him, “an outstanding and unmistakable symbol of the honesty and dignity of atheism.”

So thank you, Christopher Hitchens. You live on through the words you left behind:

To me, the offer of certainty, the offer of complete security, the offer of an impermeable faith that can’t give way, is an offer of something not worth having. I want to live my life taking the risk all the time that I don’t know anything like enough yet, that I haven’t understood enough, that I can’t know enough,  that I’m always hungrily operating on the margins of a potentially great harvest of future knowledge and wisdom. I wouldn’t have it any other way.

Using viruses to vaccinate against HIV

A new type of vaccine has been developed that could help in the fight against Acquired Immunodeficiency Syndrome (AIDS), which, according to the World Health Organisation, kills around two million people each year.

The vaccine works by infecting people with a virus that has been genetically modified to encode the DNA sequence for an antibody that protects against HIV. Once the vaccine virus integrates its DNA into the host chromosome, the protective antibody is synthesised by the cell and circulates in the bloodstream, binding to HIV and neutralising it.

Human Immunodeficiency Virus (HIV) is a retrovirus, which means its genetic code is not made of the molecule DNA, as with almost all other organisms on Earth including humans, but a related molecule called RNA. Once the virus enters a target cell, its RNA genome is transformed into DNA by a special enzyme carried within the virus particle called Reverse Transcriptase. This process was discovered by American biologist David Baltimore in the 1970s, and it caused quite a sensation because it contradicted the conventional view that biological information flows one-way from DNA, to RNA to protein (regrettably named the ‘central dogma’ by DNA’s co-discoverer, Francis Crick). David Baltimore shared the Nobel Prize in Physiology or Medicine in 1975 for his contributions to virology.

Once reverse transcribed into DNA, the HIV genome integrates with the host’s own chromosomes, and usurps cellular machinery to promote its own replication. Millions of new viruses bud off the surface of an infected cell, ultimately destroying it and causing disease.

The human immune system launches a valiant effort to rid the body of HIV, however this battle is ultimately lost almost invariably. The most significant component of this immune response is the production of killer cells known as cytotoxic T lymphocytes (CTLs), which patrol the bloodstream and destroy any cells they detect as being infected with the virus.

Vaccines often work another way, by inducing the production of antibodies, which are Y-shaped proteins synthesised by immunological cells. Each antibody has particular binding properties and recognizes a specific three-dimensional shape known as an ‘antigen’. By binding to antigens on the surface of infectious microorganisms, antibodies help protect against disease by promoting the microbe to be engulfed and destroyed by large cells called macrophages, or by physically blocking the microorganism from interacting with important molecules.

People infected with HIV produce many antibodies that bind to the virus as it travels outside of cells, after budding off the surface of infected cells and before it invades a new one.

The problem is that Reverse Transcriptase is a very imprecise piece of molecular machinery; the DNA copies it generates from HIV’s RNA template are often imperfect. In the technical jargon it is ‘error-prone’. This means that HIV can evolve extremely rapidly, as novel mutations are constantly being introduced during the virus life cycle. Thus, when the immune system develops an effective response against HIV, the virus rapidly evolves to ‘escape’ or ‘evade’ detection. Antigens recognized by antibodies and cytotoxic cells mutate so that they can no longer be recognized, and new antibodies must be recruited and refined instead. This takes time, allowing the virus to replicate without constraint. Moreover, once the new antibodies and cytotoxic cells are deployed, the virus can just evolve new antigens yet again in a continuous game of cat-and-mouse, in which the mouse always wins.

One ‘strategy’ employed by the immune system is to generate antibodies that recognize parts of HIV that cannot mutate so freely because they are structurally essential for the virus life cycle. One such region is a protein on the viral surface called gp120, which binds to a receptor called CD4 on the surface of susceptible cells. HIV’s binding to CD4, via gp120, is absolutely critical in invading host cells and thus completing its life cycle. If the CD4-binding region of gp120 were to mutate such that CD4 was no longer recognized, then the virus would be unable to infect new cells. But without mutating, if an antibody were generated that bound to this region then it would block HIV’s interaction with CD4 and promote virus destruction by immune cells like macrophages. The virus would be stuck between a rock and a hard place. So why doesn’t this happen?

HIV has evolved various strategies to ‘hide’ the conserved and critical CD4 binding region of gp120 from the reach of antibodies. Loops of amino acids hang down around gp120, which are not structurally important and thus are free to vary considerably. Viral escape variants can therefore evolve rapidly when antibodies bind to these ‘hypervariable loops’, as mutations incur little if any cost to the virus. In addition, carbohydrate molecules cover gp120’s surface like a dense forest, which are difficult for antibodies to recognize as many human cells are also covered with similar carbohydrates.

Antibodies have in turn evolved ingenious ways to access the CD4 binding region despite these measures. One such antibody, called b12, does so by use of an extended ‘finger’ – an elongated loop of amino acids projecting from its surface, that can penetrate through the variable regions and carbohydrate surrounding gp120 to reach the conserved CD4 binding site.

Antibodies like b12 are called ‘broadly neutralising antibodies’, because, by accessing critical regions like the CD4 binding area, they are capable of recognizing a broad range of HIV strains despite great variability between them.

I first read about broadly neutralising antibodies a few years ago in a stirring review article entitled ‘Antibody vs HIV in a clash of evolutionary titans’. The paper describes several antibodies that, like b12, have evolved the capacity to recognize broad groups of HIV despite the virus’ countermeasures. I remember thinking at the time that broadly neutralising antibodies would be extremely difficult to induce through vaccination. Thousands of rounds of mutation and selection had gone into generating ingenious structures like b12’s extended finger. This takes many years of continuous exposure to HIV to develop in humans; how could a single vaccination hope to induce such profound antibody evolution in a short space of time? I thought that the broadly neutralising antibodies were fascinating, but regrettably unlikely to be generated from scratch through a single vaccination.

David Baltimore’s latest paper, published in Nature, has shown how unimaginative and misplaced my scepticism was.

Not content with his Nobel Prize, Baltimore has continued working on HIV and virology and now has invented an entirely new type of vaccine, one that protects against HIV in mice.

The vaccine works by inserting the full DNA sequence of the b12 antibody into a virus called Adeno-Associated Virus (AAV) and then deliberately infecting mice with it, to transfer the antibody intact.

Like HIV, AAV integrates its genome into the host. But unlike HIV, it does not cause disease and can therefore be used as a vector to transfer new genes into an animal’s cells (AAV is being investigated for other forms of gene therapy as well).

When the transgenic AAV was injected into a mouse’s leg, its genome, including the sequence for b12, integrated with the host genome in muscle cells. These muscle cells started to produce AAV gene products including the new b12 antibody. Once in the circulation, b12 bound to the CD4 binding site of HIV and prevented newly introduced virus from invading new cells, thus protecting the mice against acquiring HIV. Baltimore’s group have named the new type of vaccine ‘Vectored Immunoprophylaxis’ (VIP). There is a short video about it available online, released by the California Institute for Technology where David Baltimore works.

Using the VIP method, mice (and hopefully people) can produce b12 without needing to develop it over years of immunological warfare with HIV; indeed, the vaccine requires no immunological response to be launched by the host at all. Muscle cells simply produce the b12 ready-made once its sequence is integrated into the host genome, and the b12 neutralises HIV by physically blocking the virus from invading new cells without requiring the recruitment of any other immunological systems. This is extra useful for an HIV vaccine, as HIV causes disease by targeting cells of the immune system causing immunospression, leading to AIDS.

Whether the vaccine will work in humans remains to be seen, but it is a fascinating and tantalizing result. VIP is yet another strategy that can be added to the armoury for scientist’s continuing struggle to develop vaccines against deadly infectious organisms, and represents a major breakthrough in both vaccinology and gene therapy.

Look to Lions, not Lambs, for the Origins of Human Tapeworm

Tapeworms that plague humanity originated in carnivores such as lions and hyenas, and jumped to humans after we began eating their prey animals on the African savannah.

This contradicts the long-held view that humans acquired tapeworms from our domesticated livestock, cattle and swine, following the agricultural revolution around 10,000 years ago.

In a 2001 paper by Eric Hoberg and colleagues working at the United States Department of Agriculture, genetic analysis of a wide variety of tapeworm species found that the human-infecting varieties were most closely related to those that infect modern lions and hyenas (1).

Tapeworms are a large group from the so-called ‘flatworm’ family (known technically as the platyhelminthes), which are relatively simple creatures with no body cavity, heart, circulatory system or lungs. They are evolutionarily simpler than the unrelated but misleadingly similarly named ‘roundworms’ (also called nematodes), which also parasitize humans and animals.

The main tapeworm species that infect humans are Taenia saginata, Taenia asiaticus (both beef tapeworms), and Taenia solium (the pig tapeworm).

Like most tapeworms, these parasites have a relatively simple life cycle involving a definitive predator host in which the adults live, and an intermediate host in which juveniles reside as tissue cysts called cysticerci. When the predatory definitive host eats (undercooked) meat infected with cysticerci, the cysts hatch and adult worms can grow to meters in size in the definitive host’s intestines, producing eggs which pass in the faeces and are eaten by the herbivorous intermediate hosts, whereupon cysticirci form in the tissues and the life cycle is completed.

Humans act as the definitive host for T. saginata and T. asiatica by eating undercooked beef infected with tapeworm cysticerci, and likewise for T. solium by ingestion of undercooked infected pork. The adult worms cause relatively little disease other than mild gastrointestinal discomfort, and can be asymptomatic. They produce eggs at a prodigious rate that are continuously shed into the environment through faeces.

But humans can also act as intermediate hosts following ingestion of tapeworm eggs from the contaminated environment. Cysticirci can then form anywhere in the body, including major internal organs such as the heart and brain, causing heart failure in the former and epilepsy in the latter. Cysticircosis, as it is known, can be fatal.

Scientists traditionally adopted an ‘anthropophilic’ view in which humans acquired T. saginata and T. asiatica from ancestors of cows, and T. solium from ancestors of pigs, following the domestication of these species. But Hoberg’s work turns this on its head: one of the closest relatives to T. saginata and T. asiatica is T. simbae. As you might guess from the name, this is a tapeworm whose definitive host is the African lion (‘simba’ is Swahili for lion). T. simbae cycles between antelope and lions in a typical predator-prey lifecycle. Similarly, the closest relative of T. solium is T. hyaenae, which cycles between the predatory hyena and various prey species including Impala and the Sable antelope.

The implication is that humanity acquired these tapeworms following a shift in diet from herbivory to omnivory; we started eating the same big-game African prey animals as lions and hyenas did, and thus became another definitive host for the worms. Indeed, this may well have pre-dated the origin of our species, Homo sapiens, going back as far as 2 million years to the origin of the genus Homo.

It is thought that climatic change brought our ape ancestors out from the forests into the open plains, where they could have incorporated big-game meat into their previously mainly herbivorous diet.  Perhaps relying on scavenging from kills by hyenas and lions at first, species such as Homo habilis (the first tool-user, or ‘handy man’) and Homo erectus subsequently developed the skills needed to hunt prey for themselves, and our digestive physiology evolved accordingly.

According to this view, humans only recently infected our domesticated livestock with the tapeworms we had acquired from African game much earlier, T. saginata and T. asiatica entering cattle as the new intermediate host and T. solium cycling through pig meat.

Furthermore, given that humans can act as both definitive and intermediate host for T. solium, Hoberg reflects that cannibalism amongst our ancestors may have enhanced the transmission of this parasitic tapeworm, cycling between intestinal adults and tissue cysts in the same species.

So pigs and cows should be blaming us for infecting them with cysticircosis and not the other way round! A fantastic finding, and one discussed in Alice Roberts’ latest superb BBC series on human evolution, Origins Of Us.

(1) E P Hoberg, N L Alkire, A de Queiroz, and A Jones.Out of Africa: origins of the Taenia tapeworms in humans. Proc Biol Sci. 2001 268(1469): 781–787.
doi:  10.1098/rspb.2000.1579

On the Merits of Mating with Neanderthals

Regions of the human genome pivotal for orchestrating immune defence against infectious organisms have been inherited from Neanderthals and their close relatives, according to a study by Laurent Abi-Rached (at Standford University School of Medicine) and colleagues (1).

The archaic genes are located on chromosome six in modern humans, at the ‘Major Histocompatibility Complex’, or MHC. First identified in the 1950s as being responsible for acute tissue rejection following organ transplantation, the MHC is now known to encode several genes involved in immune defence. These include the Human Leukocyte Antigens (HLAs), which display small fragments of pathogenic organisms (or transplanted organs) on the surface of certain cells. These ‘antigens’ are then detected by cells of our immune system, so that the original infectious organism can be destroyed.

Amazingly, several HLA gene variants found in modern humans bear a striking resemblance to those isolated from the remains of ancient Neanderthals and their close relatives, the Denisovans. These HLA types are now only found in people from Eurasia and the Asia-Pacific region, and are absent in Africa. The most parsimonious explanation is that Neanderthal genes entered the human gene pool of European and Asian humans following interbreeding between the two species, sometime after humans left Africa around 80,000 years ago. Hence, modern Europeans and Asians inherited the Neanderthal genes while modern Africans did not.

Neanderthals are archaic hominids that inhabited much of Europe from about 400,000 years ago to 30,000 years ago, when they abruptly disappeared. Unlike their cartoonish ‘cave-man’ portrayal by the media, Neanderthals possessed brains similarly sized to modern humans, and genetic analysis has shown they possessed a variant of the FOXP2 gene known to play a role in language in modern humans. It seems reasonable to assume they were comparably intelligent to us.

The Denisovans are a recently discovered group of ancient hominids that were probably closely related to Neanderthals, and are known archaeologically only from isolated sites in Siberia that date to 40,000 years ago.

Anatomically modern humans evolved in Africa several hundred thousand years after the Neanderthal/Denisovan ancestor left that continent headed for Eurasia. But, sometime between 40,000-80,000 years ago, a group of humans left Africa and spread out across the globe, diversifying into all the current non-African peoples on Earth. During this mass migration, our human ancestors undoubtedly come into contact with the Neanderthals and Denisovans that had already inhabited Europe and Asia for over 200,000 years previously.

Svante Pääbo and colleagues at the Max Planck Institute for Evolutionary Anthropology, in Germany, sequenced much of the Neanderthal (2) and Denisovan (3) genomes using bones from ancient caves. They showed conclusively that Neanderthals and humans had interbred, with Neanderthal DNA contributing 1-4% of modern Eurasian genomes, and Denisovans contributing 4-6% of modern Melanesian and Australian Aborigine genomes. The latter result was particularly surprising given that archaeological remains of Denisovans are only known from Siberia. The presence of Denisovan DNA in modern Melanesians and Australian Aborigines suggests that the Denosovans once enjoyed a massive home range, from freezing Siberia in the North to the tropical Asia Pacific in the South.

Earlier this year, Vania Yotova and colleagues reported that a region of the human X-chromosome unique to Europeans and Asians was more similar to Neanderthals than to modern African people (4). This suggests that the region (known as a ‘haplotype’ to geneticists) was inherited from Neanderthals by Eurasians following interbreeding, and hence Africans do not possess it. The authors concluded that,

 “Considering such early encounter of H.sapiens with Neandertals, a question may be raised: was this encounter coincidental and without important evolutionary consequences or (either through genetic or cultural exchanges, or both) did it facilitate adaptations to novel environmental conditions that actually contributed to the successful expansion of human migrants from Africa to other continents?”

This is a fascinating question. In essence, it asks what the functional consequences of Neanderthal and Denisovan interbreeding were for European and Asian people, if any.

This latest article in Science answers the question: interbreeding may have helped the Eurasian immune system to combat local pathogens that the migrating people had not encountered while in Africa.

The Neanderthals and Denisovans, having lived on the Eurasian continent for several hundred thousand years, would have been better adapted to the environmental conditions there than the modern humans only just leaving Africa. In particular, their HLA genes would have been naturally selected to optimize presentation of antigens from local infectious microorganisms to the immune system. In other words, their immune defence was more finely calibrated to tackle the regional microbes.

After mating with Neanderthals and Denisovans, these well-adapted-for-Eurasia HLA gene variants entered the human gene pool and would have been naturally selected for amongst humans, because they provided better protection against Eurasian pathogens than the ancestral Africa-derived alternatives did.

For example, a particular HLA variant called HLA-A*11 was found commonly in Neanderthals, Denisovans and modern Asians but rare elsewhere and nearly absent in Africa. The HLA-A*11 gene provides better protection against a particular virus called Epstein-Barr Virus (EBV), which causes glandular fever in adults and can contribute to the development of certain cancers. Other HLA types of Neanderthal or Denisovan origin help to activate a type of cell called Natural Killer cells, which are known to destroy virus-infected cells.

In addition, mating with archaic hominids from a different species would have helped restore variation in the human genome. Variation was lost in all non-African humans because we all descend from a small group of Africans that left the homeland 40-80,000 years ago. The global non-African human genetic diversity thus falls within a subset of the much larger genetic diversity still seen in Africa.

Genome variability plays an important role in immune defence, and is known as ‘heterozygote advantage’. By having a variety of HLA genes, a wider range of infectious organisms can be detected by the immune system, making it is less likely that a microbe will ‘slip through the net’ and cause severe disease. Natural selection thus operates to maintain variation, known technically as ‘heterozygosity’, in HLA genes. (This type of natural selection is also known as balancing selection.)

Following the tight population bottle-neck in which every non-African on the planet descended from a small group of African humans, heterozygosity in HLA genes was reduced in non-African populations. Mating with members of different (albeit closely related) species would have helped to restore variation by shuffling more HLA varieties into the available gene pool.

These studies show that Neanderthals and Denisovans never truly died out, for aspects of their genetic makeup are still found today in non-African humans. Wherever human people encountered archaic hominid populations, they bred with them; from Asia-Pacific people meeting Denisovans to Europeans encountering the Neanderthals. Moreover, some of the genetic exchange between these different species helped non-African people to survive the local conditions, surely quite different from their African homeland. In particular, HLA genes involved in pathogen recognition derived from Nanderthals and Denisovans entered the human gene pool following interbreeding and subsequently spread by natural selection, owing to the advantages they gave in combatting the local infectious diseases.

What a religious person would make of these findings, incidentally, I find intriguing. Did Neanderthals and Denisovans have souls? If not, then did the offspring of Neanderthal-human crosses possess souls? If hominid hybrids are not counted as human then large sections of modern non-African people must also be excluded, descending as we do from distant Neanderthal and Denisovan ancestors.

And if it is conceded that Neanderthals and Denisovans did possess souls, it seems a rather extraordinary omission from mainstream Christian theology that heaven and hell is crammed with the souls of holy and damned Neanderthals as well as humans. Or do the different hominid species get sent to separate afterlifes? (In which case, where did the first hybrid children get sent- Neanderthal or human afterlife?) Moreover, how far back in the evolutionary tree do you have to go before animals become soul-less? How about Homo erectus, from which both Neanderthals and humans probably descend? Or Lucy’s species, Australopithecus afarensis? Do chimpanzees and gorillas have souls, with whom we share a very recent common ancestor?

Of course a non-believer need not worry about these questions. But I am genuinely curious how a religious person would answer them, and why they aren’t debated more frequently in religious circles.

Anyway, genetics is awesome and I am probably part Neanderthal. Good times.

(1) Science 334, 89 (2011); DOI: 10.1126/science.1209202

(2) Science 328, 710 (2010); DOI: 10.1126/science.1188021

(3) Nature 468; 1053–1060, 2010. doi:10.1038/nature09710

(4) Mol Biol Evol (2011) 28 (7): 1957-1962. doi: 10.1093/molbev/msr024