Biotech must be some brilliant science

I quite liked this comic (hat tip to Pharyngula):

While I was reading this, I was reminded of an interview with the chief scientist of Advanced Cell Technologies, Robert Lanza. The interview, titled “Fighting for the Right to Clone” (where clone unfortunately only includes therapeutic cloning), is subtitled:

Stem cell and cloning guru Robert Lanza has battled the Catholic Church, the White House, and violent protesters.

And later speaks of his time at Advanced Cell Technologies, and the dangers he faced:

[Lanza] At the time, ACT was a subsidiary of a poultry genetics company, doing work in agriculture. When I joined they made the move from animal cloning to human therapy, and we knew we would get hit, big-time. I may be the only person who’s had the [Catholic] Church, the pope, and a couple of presidents condemn my work. At one point we had bodyguards here. There was a bombing up the street; then a doctor at a local in vitro fertilization clinic was targeted. I didn’t think I would be alive for more than a few years.

[Discover] And you, alone on your island, were so vulnerable to attacks.
[Lanza] I would go for a walk, listening for sounds. I was one of the most visible people in cloning and yet I was isolated. I figured there was more than a 50 percent chance that I would be knocked off. But I wanted to go out trying. I’ve always followed my heart.

Hmm, condemned by the Pope, various churches, presidents of various nations, and at a good risk of being bombed. If that comic is anything to go by, biotechnology must be some brilliant science.

Mice reject human embryonic cells – so what?

Researchers at Stanford University School of Medicine found that mice mounted an immune response after being injected with human embryonic stem cells (hESCs). The result: all the transplanted stem cells—which hold the promise of maturing into several different types of tissue—were dead within a week [from Scientific American].

All of this is leading many to claim that embryonic stem cells won’t work. But that is is big stretch from the data in that study.

First, this study examined human cells implanted into mice. Mice are not the same as humans. The genetic difference there is obviously going to be a factor. That said, it is true that mice have also rejected murine embryonic stem cells (Wu et al 2008), but some research has shown that mice are more likely to develop a tolerance to embryonic cells than to other transplanted tissues (Robertson et al 2007).

Second, scientists already thought this would happen. It is for that reason that the whole concept of therapeutic cloning was considered. If the embryonic cells were genetically identical to the patient, the immune system would likely not attack those cells.

That said, therapeutic cloning still leaves the 16 genes that are present in the egg donor’s mitochondria. It is possible (though, considering that these genes are not cell-surface proteins, unlikely) that this slight difference could still cause an immune response. This has lead some to tout induced pluripotent stem cells as an answer, but those cells are genetically modified in order to induce their pluripotency, so not even they are identical.

I think that both therapeutic cloning and induced pluripotency will be solutions to this immune problem, although I personally would favour the genetic modification of the immune system to stop it being so reckless and killing that which is trying to help. After all, those of us who suffer from autoimmune diseases know that the immune system can quite easily attack cells which are genetically identical to all your other cells.

Rat brained robots and reporters

As news stories have been reporting for the last 36 hours or so, researchers at the University of Reading in the UK (home of the Project Cyborg, led by Prof. Kevin Warwick) have made a robot controlled by rat neurons.

But many reporters, being fundamentally rat-brained themselves, have made the mistake of saying silly things like these:

To build the cyborg, Warwick, his colleague Ben Whalley and their team dissolved a fetal rat’s brain. They then put the free-floating brain cells, or neurons, into an electrode-ringed Petri dish, where the cells quickly reassociated with each other and began randomly firing electrical signals. Electrical pulses sent through the ring of electrodes calmed down the neurons, and after a while the cells began to “learn” patterns among the external pulses. [from FOXNews]

Now the reason there are quote marks around the word “learn” is because it didn’t really happen.

It is true that a network of 300,000 murine neurons (i.e. rat brain cells) are controlling that robot through 80 electrodes. It’s true that the cells, which were dissociated in solution, spontaneously formed that network (which was, in my opinion, the most exciting part). But it is not a robot controlled by a rat’s brain, for these are only brain cells – admittedly forming a primitive brain, but not a brain anything like that of a rat.

And it is most certainly not true that these neurons learnt how to control the robot – the researchers set up the robot and electrodes so that whenever the sensors detected a wall, it sent a 1 volt pulse to the neurons in the dish. And the neurons, being fully functional, were elicited into giving off an action potential. Just like neurons do when hit with an electrical stimulus of 1 volt (which is massive for such small cells, by the way). And this action potential, after it had been transmitted through a few neurons, was recorded and used (by a computer) to make the robot turn away from the wall. It is not the neurons in the dish that learnt to control the robot, but the computer that is reading the activity of those neurons (and the programming of that computer by human brains).

From a neuroscience perspective, the neurons have not learnt much. They have probably strengthened their connections to the electrodes, but it is a far cry from learning to control the robot. Those 300,000 neurons aren’t really doing much that the 302 neurons of the nematode worm C. elegans couldn’t do – in fact, they are probably doing far, far less.

Aside from the fact that the neurons formed a network spontaneously, I am unimpressed.

UPDATE: Steve Potter, a neuroscientist from Georgia Institute of Technology has commented on the blog Neurophilosophy, saying:

I see nothing new here beyond what we and others have been doing for the past 5 years. Believe what you read in peer reviewed papers.

So that explains why I, being a neuroscience student, wasn’t at all impressed.

Photosynthetic people

I was reading a recent article – “Changing the nature of human beings” – by Julian Savulescu in the Sydney Morning Herald, and he mentions this:

So one day we could have people with sonar like bats, or people with the ability to create their own energy by photo-synthesising sunlight like plants.

Elysia ornata

At first I was dismissive of the idea of solar-powered people, but then I remembered reading in a marine biology pamphlet that certain sea slugs are ‘solar-powered‘. I investigated that some more, and it does turn out that certain molluscs have a symbiotic relationship with chloroplasts that they steal from the algae they eat, which – like plants -are organisms that normally utilise chlorplasts. (Rumpho et al, 2000). One molluscan slug species, Elysia chlorotica, can survive for up to nine months without eating: just on light and carbon dioxide (Green et al, 2000), and even then the slugs die of old age not hunger. Still, the chloroplasts die after about six to ten months, and need to be replenished by eating more algae.

Chloroplasts are solar-power plants of the plant cell, just like the mitochondria that animals and fungi rely on (plants have mitochondria too though). Just as mitochondria were once proteobacteria, plastids (of which chloroplasts are the most noteworthy) were once cyanobacteria, and both still have their own DNA and a very bacteria-like membrane. They have evolved to get very comfortable with the relationship, offloading much of their essential genes to the host nucleus, and now they can’t live without their hosts (then again, we can’t live without our endosymbionts).

This means, however, that if we humans wanted chloroplasts for ourselves, or our livestock or pets, we would need to genetically modify the host animal to express proteins required for chloroplast function. It has been estimated that about 70-90% of the genes required for chloroplast function are provided by the plant’s genome (Martin et al, 1998). In the case of the sea slugs, some of these genes appear to exist in the animal’s genome, although probably not enough for the chloroplasts to be able to reproduce. Which is why the slugs use kleptoplasty – removing the chloroplasts from their food.

It would probably be most feasible for chloroplasts, along with the required genes, to be added to skin stem cells and applied as a skin graft, as there is a lot of research in this area for burns victims. This approach has been used to produce proteins in mice (Larcher et al, 2001), and so should be feasible for producing sugar by photosynthesis in humans. At first this graft may require regular replacement, but eventually the chloroplasts will be sustainable within the skin.

There are a few problems (the 5th problem is, in my mind, the biggest too).

1. The immune system may attack the chloroplasts, but maybe they will be safe from antibodies if they are inside the cell (the immune system will attack mitochondria, but only if they are present in the blood).

2. The photosynthesising skin would necessarily be green as that is the colour of chlorophyll. I suppose the melanocytes of human skin could be engineered to produce another pigment, causing the skin to take on a different colour, but then again it might not be such a big problem to be green skinned…unless you are sensitive to Bruce Banner jokes.

3. People may get sunburn and skin cancer when they are out ‘feeding’ on sunlight, as while the red and blue parts of light will be used, the ultraviolet component of sunlight causes damage to living cells. To absorb this before it causes damage, vertebrates have melanins (and humans augment this with sunscreen), and plants/algae (which don’t use UV light) produce screening compounds. It is likely that a derivable sunscreen pigment, which does not darken the skin like melanin, could be produced by melanocytes and absorb the UV-B light. But the idea of endogenous sunscreen is beside the point of this post (to be dealt with another time).

4. The reaction of photosynthesis can be simplified as the following:

6 CO_2(g) + 12 H₂O_(l) + light → C₆H₁₂O_6(aq) + 6 O_2(g) + 6 H₂O_(l)

It is now obvious why plants need to be watered – there is a net loss of six water molecules for every glucose molecule produced. This would mean that the plant-person (or algae-person) would also need a lot more water than a normal human, which would be a disadvantage in a desert environment.

5. It wouldn’t produce much energy for an active organism like a human. The average human being has 1.8m² of skin, approximately half of which would be exposed to the sun (if naked and lying as you would if tanning). The Earth is bathed in much energy from the sun, but of that solar radiation only the wavelengths from 400-700nm are usable by plants (termed photosynthetically active radiation, or PAR). Even at midday on a very sunny day, the PAR energy flux density (or, the amount of plant-usable light energy per unit area of ground per second) is only 400W/m² (Warrington, 1978). Photosynthetic efficiency (amount of light energy converted into usable chemical potential energy) typically is about 3-6%, so let’s assume 5. So the energy produced by a human being lying in the sun for an hour (3600 seconds) at midday would be:

400 J/s/m² x (0.5 x 1.8m²) x 0.05 x 3600s = 64800J = 64.8kJ (or 15.43 kcal)

By comparison, an apple has about 400kJ of usable food energy. So an hour in the sun is about the same as a sixth of an apple. The daily energy requirements for a human being sit around 10,000 kJ per day, so that’s going to require 150 hours per day of sitting in the sun. Needless to say, that’s impossible.

This apple can give you as much energy as an entire day's worth of photosynthesis.

So, although photosynthetic humans would need less food, it wouldn’t be substantially less. Still, over a large population, it could slightly reduce the need for farmland. In addition, as I alluded to earlier, this could be done to livestock too, and with a large number of livestock that could noticeably reduce the area of land required to feed cattle or horses (hairy animals like sheep or sensitive-skinned animals like pigs may be more difficult, as the hair would reduce the light available for photosynthesis).

So, solar-powered photosynthetic people are possible, but it wouldn’t significantly alleviate food requirements…but it might make a little bit of a difference, until the sun burns out or is clouded out by pollution or something.

Image credit:

The image, of the sea slug, is of the sacoglossan slug Elysia ornata. It was taken by Flickr user budak, and released under Creative Commons BY-NC-SA license.

Olympic Enhancements

The Olympics are upon us, and so are the many articles on the horribly unacceptable spectre of GENE DOPING!!!1!. Oh how contrary to the athletic goal it is to try make your own body better than the bodies of your competitors. How dare they try to run faster or longer, jump higher or farther or concentrate better!

I give a list of the recent articles on the subject, plus a bit of my own commentary on the viewpoints expressed by the authors.

The ‘exercise pill’

Ron Evans and his team developed a pill that can mimic the effect of exercise, or increase exercise’s impact, on muscle endurance. I’ll talk about the science behind this another time, but suffice it to say it isn’t really exercise in a pill – just an endurance enhancer in a pill. It is important to note that Evans developed blood and urine tests for the constituents of the pill and gave it to the World Anti-Doping Agency (WADA). Fair enough – such a pill would be against the rules – but I think this is a dangerous precedent. Could scientists be expected, some time in the future when academic or health enhancements are against the law, to make all enhancements easily detectable? It’s a recipe for “gene-ism’ in my opinion.

Enhancements are just natural

Andy Miah, whose blog has long been on my blogroll, has an article in the Washington Post that is actually pro gene-doping. Unfortunately, I think his reasoning leaves a bit to be desired. First, the title of the piece – “Enhanced Athletes? It’s Only Natural” – seems to close to the fallacy of ‘appeal to nature’ (if it is natural, it is acceptable). Though seeing as this fallacy is often used in arguments over this subject, perhaps it is appropriate to fight fire with fire.

Also, consider this paragraph:

By today’s standards, if most of us non-athletes took a random doping test, we’d probably fail it. Few consider this to be morally troublesome. For most of us, human enhancement is an essential part of daily life: We enjoy ultra-whitening toothpaste, vitamins, anti-aging skin cream, daily doses of caffeine and much more. We’re already enhancement junkies. So why should athletes be restricted in carrying out their daily tasks — such as breaking world records — when the rest of us are unimped in gaining a competitive edge at the office by, say, drinking coffee?

This is merely pointing out contradictions in the way we act, which does nothing to get to the underlying issue of whether enhancements are acceptable. It could very well be that caffeine in the office will soon be banned. Nonetheless, I applaud Andy Miah for putting himself out there on the pro-doping side of the argument. It should create some discussion, at least.

Amateurs cheat like the pros

Another article in the Washington Post tells how amateurs are using performance-enhancers. But amateur sportspeople seem to be amateur enhancers too, using enhancements like “painkillers, caffeine (in pill and standard liquid form), decongestants and asthma drugs”.

But most amazing, I think, is this quote about a comment made by internist Gary Wadler, who works with WADA:

Caffeine, unregulated by WADA, is up for reconsideration as a banned substance, Wadler says.

So, no coffee or energy drinks in the Olympic Village? Maybe.

But back to the amateurs, there are two options. You can either test all the competitors, or you can educate people about the risks or ethical issues and hope they listen. Given the ever-present desire to win, and the coming advances in diagnostic technology, I think I know what will happen.

The race against gene doping

Though not in a high-profile publication, I found this article on SignOnSanDiego.com to be interesting. It discusses the future of WADA’s efforts to catch the genetically enhanced. They want a bioinformatics approach, with supercomputers collecting all the data on the genomes, proteomes and metabolomes of athletes and checking to make sure they don’t cheat. In other words, they will be banned if they get too good.

I like this quote:

Thomas H. Murray, president of The Hastings Center, an independent bioethics research center based in New York […] said, gene doping violates WADA rules and the general sense of what constitutes fair play. “It’s ethically wrong, no different from illegal drug use,” he said.

And fighting it is also going to be no different to fighting illegal drug use. And we all know how effectively we’ve wiped the Western World clean of drugs…

And this:

Some observers have argued that gene transfer is OK, that it simply levels the playing field, potentially providing every athlete with roughly the same biological equipment.

Murray argues otherwise. Even if gene transfer were to become widely available and commonly used, he said the technology would have no place in sports. Who would decide which inherited, physical characteristics could be genetically altered, he asked. And where would the line be drawn?

A line? Who said anything about a line?

Andy Miah…again

Another statement by Andy Miah was reported in an article on gene doping the British newspaper Evening Standard. This time, he says this:

There is no other technology that is likely to change the Olympics [more] than gene doping. It’s not possible to detect and there’s a good chance that it will never be detectable in any meaningful sense. This forces the world of sport to reconsider what it does about testing. It’s time for their plans to change. It’s time for the era of human enhancement to take full effect in the Olympics.

This is not necessarily good ethics. Just because something will happen, that doesn’t mean it should be accepted. I don’t like this portraying of gene doping as a “major headache” that we just have to live with. He also makes an appeal to antiquity by saying:

There has never been a ‘clean’ Olympics.

While this is probably true, because even the ancient Olympians were on performance enhancers (like eating ram’s testicles as anabolic steroids), it’s hardly a good reason to accept an unclean Olympics. No, we need to argue that enhancement is as much a part of the ‘spirit of sport’ as any other training or dietary program, and indeed is as much a part of being human as talking or walking.

Technical hurdles in gene doping

A New Scientist article on the mechanisms of gene doping point out the difficulties involved. First, viral vectors are not efficient and are not yet accurately targeted, so may cause cancer if used. Second, plasmids are even less effective, meaning so few cells would receive the gene that it would be useless to even try.

The article also looks at an interesting take on detecting the ‘undetectable’:

WADA will soon be looking for the physiological consequences of cheating, rather than for substances themselves. Each athlete will serve as his or her own physiological index, providing baseline patterns of gene activity, protein production and metabolic activity against which any drastic changes can be spotted.

Which, as I said before, is just banning people from improving too much, but allowing them to improve slowly. Seeing as this is just a matter of degree, not of kind, one has to wonder what is so wrong with improving performance quickly that doesn’t apply to getting better slowly.

GMO – Genetically Modified Olympian

A story also appeared in The Economist about genetic enhancement in sport. It reviews many of the genes that could possibly appear in early athletic genetic enhancements, like EPO (gene that produces erythropoetin, a protein controlling red blood cell production), MSTN (gene that produces myostatin, which controls muscle growth) and PPRD (produces Peroxisome proliferator-activated receptor delta, which controls metabolism in skeletal muscles). Also discussed are endorphins, which could reduce pain felt during competition or increase incentive to exercise.

The article also discusses in-depth the moves made by WADA, which banned:

“the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance”

And puts millions of dollars each year into trying to enforce that. The article discusses the two ways WADA can do this – detect the vector or gene that has been inserted, or detect the change in physiology produced by that insertion.

Gene doping – fair and safe

This opinion piece follows the previous piece in The Economist, and it is surprisingly for genetic enhancement (with regulatory oversight and the like, of course). It takes a sensible view: of the two reasons for banning genetic enhancement- safety and fairness – only the former makes any sense. That is because athletics doesn’t appear to try to be fair at all.

First, unfair natural genetic gifts are allowed. This is demonstrated in the opinion piece by the following example:

Eero Mantyranta, a Finn, was a double Olympic champion in cross-country skiing. His body has a mutation that causes it to produce far more of a hormone called EPO than a normal person would. This hormone stimulates the production of red blood cells. A synthetic version of it is the (banned) drug of choice for endurance athletes. Mr Mantyranta was allowed to compete because his advantage was held to be a “natural” gift.

Second, countries are not required to have fair training facilities or coaching. Again, from the article:

Some point out, for instance, that it would help big, rich countries that have better access to the technology. But that already happens: just compare the training facilities available to the minuscule Solomon Islands squad alongside those of mighty Team America.

I also find it interesting that comments on this opinion piece rightly point out that athletes are just humans, so if we ask whether athletic enhancement is allowable, we are really asking whether human enhancement is allowable. Sport is just the tip of a much greater iceberg.

Podcast on sports enhancement

This last one is not a news piece, but an up-and-coming podcast on the issue. It will interview Arthur Caplan (a moderate bioethicist who is mostly anti-enhancement), Gary Wadler (who works with WADA, see the section in this post about Amateurs cheat like the pros) and Michael Werner (head of the biotechnology consulting firm, The Werner Group, and from what I can tell, mostly pro-enhancement). If they put up a podcast, I’ll put my thoughts up on this blog.

UPDATE:

There is also a new article in the New York Times titled “Let the games be doped“. The author, John Tierney, is after suggestions for what a pro-enhancement games could be called. Give your suggestions here.

Gene doping is more fair, not unfair

Gene doping – the enhancement of athletic ability by genetic manipulation – is a big issue around the upcoming Olympic games in Beijing. The hippies at Friends of the Earth have decried the practice of gene doping in a recent press release. Gillian Madill, a genetic technology campaigner, said this:

“Altering one’s genetic makeup to impact athletic performance is unacceptable. Gene doping is cheating, and it’s dangerous. Professional sports organizations should ban it. All athletes deserve to compete on an even playing field. Gene doping undermines that right.”

“Friends of the Earth opposes all genetic modification of life, including human life. It is important to protect the gene pool, our most basic common natural good, from genetic pollution caused by genetic engineering. It is impossible for humans to comprehend the implications of manipulating the genetic makeup of nature.”

It should be obvious to anyone who has read this blog for more than five seconds that I completely disagree with almost everything she said.

I fully acknowledge that gene doping is unaccepted, but not that it is unacceptable. Gene doping is cheating only because it is against the rules, not because it is inherently unfair. It is dangerous though, I will agree with that (and with a ban against it, it can only get more dangerous).

But that’s not the worst part (by worst, I mean most obviously wrong). Madill says that gene doping undermines the athletes right to compete on a level playing field. Unbelievable. I’ve already talked of this argument before, so now I can do no more than quote Julian Savalescu:

“Sport discriminates against the genetically unfit. Sport is the province of the genetic elite (or freak). […] By allowing everyone to take performance enhancing drugs, we level the playing field. We remove the effects of genetic inequality. Far from being unfair, allowing performance enhancement promotes equality.”

The most level playing field possible would occur when all athletes have a standard body and a standard genome, much like motor racing does with standards on their cars. If it’s a level playing field you want, then how can you justify keeping the natural inequality that pervades athletic competition?

As for the last part on genetic technology in general, I am reminded that one man’s ‘pollution’ is another man’s enhancement. I’ll keep my genes out of the human gene pool if necessary, but I reserve the right to ‘pollute’ my own body. And everyone else can do the same.

I also don’t think it is “impossible for humans to comprehend the implications of manipulating the genetic makeup of nature”, but I will admit that we don’t know everything about the implications. That is a reason to use caution, but not at all a reason to stop genetic technologies altogether. After all, we don’t know the implications of banning genetic technologies, so maybe Madill should follow her own advice and ban the ban (then again, she doesn’t know the full implications of doing that either).