International study: What should happen to your genomic information?
Would you want to know your likelihood of getting certain diseases? With genome tests, how much information does the public really want to know about themselves? How much informations should clinicians and researchers reveal to the patient or clients? These are relevant question even today, but will become more so as we start to dig deeper into the mysteries of the genome.
Wellcome Trust Blog: 1 February 2012 – The survey
Genomic researchers, used to working with anonymous samples, are facing increasing pressure to share their findings with the volunteers who provided their samples.
There is now an urgent need to understand what the public and professionals want in terms of feedback of genome data. With this in mind, the Wellcome Trust Sanger Institute are asking people: what would you want to know?
They are conducting an international study to explore some of the ethical implications of whole genome evaluation, in what they hope will be the largest survey of its kind.
More also at Genomeethics
Nanotechnology and the fight against cancer
From diagnostics to drug delivery, clinicians want to take selective aim at tumour cells
The Guardian: 31 January 2012
UK sets sights on gene therapy in eggs
Public consultation and safety assessment would pave the way for embryo manipulation to treat genetic diseases.
Nature, 24 January 2012
Early promise for human embryonic stem cell therapy
Two clinical trials testing the eye’s retinal cells derived from human embryonic stem cells report positive preliminary results.
Nature News Blog: 23 January 2012
Other media reports:
Note that the Reuters article doesn’t mention that the eyesight improvement in one patient was thought to be due to the placebo effect
Two tribes at war. What The Atlantic’s very real dangers of GM food reveals about us.
By Jason Major
TechNyou
The Atlantic which ran the article, “The very real dangers of genetically modified foods”, by Ari Levaux has unleashed an unusually massive online response. The reasons seem to be many, but I would suggest it starts with the journalist’s complete mangling and distortion of the science that produced a misleading, even deceptive article. The result was 334 comments, at last count, some from TechNyou. An analysis of this commentary reveals the obvious two distinct tribes fighting trench warfare at a stalemate, but more revealing was the difference in their tactics, which might be indicative of why this debate never moves forward..
The ample commentary tearing apart Levaux’s faulty analysis and interpretation has forced him to rewrite his article and I won’t repeat the criticism of the article from others more qualified than myself. Nevertheless because Levaux’s claims the main point of his article was to point out the inadequacy of substantial equivalence as a tool to assess the safety of GM foods, calling it an outdated and an unproven hypothesis, at the end of this post I have included some of his points and the key responses to it. I have done this largely because Australia’s regulators also rely on substantial equivalence as their key assessment tool for GM foods.
Two tribes
I thought I would take a different tack with a dissection of the commentary rather than the article itself.
There are two distinct and obvious tribes: those in favour (or at least not vehemently opposed) to GM Foods, and those against it. The interesting this is the difference in tactics. Each fight with different weapons that pitted against each other appear to neutralize themselves, so that neither side gains ground.
The following is my quick and subjective analysis of the commentary. I sorted the comments into those obviously arguing in favour of GM foods and those arguing against them. Within the ‘in favour’ and ‘against’ I split them again into additional categories: those making commentary using scientific evidence to support their arguments and those using value-based judgements to support their arguments. I also had a category for those that appeared neutral. I didn’t review all the comments because basically I got bored, but I got through close to two-thirds of them. There were a few threads I ignored because they were the same two people going tit-for-tat: you’re wrong; no you’re wrong. There were also other ignored comments that were simply along the lines of, “you are a nutter”.
In the ‘in favour’ camp under scientific arguments I made a third category: ‘science neutral, which is explained below.
The categories
In favour of GM food
Scientific argument
Examples:
see comment from Karl Haro Von Mogel toward end of post
Or, “We know where the proteins in a genome are by sequencing messenger RNA that is in the cell and matching it up to the genome. We know where the miRNAs are by sequencing short RNAs that are in the cell (those that are about 21 bases) and matching them up with the genome… In humans, the miRNAs are generally in between genes, or within genes in the part that gets spliced out (the introns). In plants the miRNAs are generally not within genes at all…”
Values argument
Example: “I understand why Monsanto tried to use the Terminator gene system, because I understand intellectual property. A company can’t give something away for perpetual use for a one time fee.”
Or, “Yes, I suppose I could be worried that every funny looking potato in my garden is a dangerously toxic mutation, but part of being rational is sticking your head in the ground and not letting your life be consumed by worry over every trivial risk.”
Science neutral
This category was included because there were a number of comments from people who in previous posts appeared to, in principle, support GM food, though taken in isolation such comments would have appeared neutral because in this case they simply stated the science without appearing to use them to support or denigrate GM foods.
Example: “The word *can* is important here. Just as you say the substantial equivalence concept is a hypothesis so is the idea that GMO foods can cause metabolic disorder. This idea has never been demonstrated. I’m not saying GMO is great but if you are going to use science to demolish an opponents argument you should apply the same standards to your own.”
Against GM food
Scientific argument
I could have split this category again because there were about five comments using false or misunderstood assumptions about the science, such as the 1st example below. But I decided to lump them all together.
Examples: “But whereas organic apples and non-GMO are selected over a period of decades, GM food is spliced with viruses including Ebola. Not sure I like the idea of consuming that.”
Or, “genetic engineering can cause changes in metabolism that are much more extreme than mere cross breeding. This is because genetic engineering depends on DNA expression promoters and the introduction of completely novel proteins into organisms that have never produced them before.”
Values argument
Examples: “I disagree*. Evolution isn’t motivated by profit.”
Or, “Sadly, every decision made by big business is based upon the bottom line rather than the common good. Until this mentality changes, we are doomed to endure that which will benefit commercial interests.”
Neutral
This covers a lot of commentary, and some may not necessarily be neutral, but they appear to be so relative to the GM issues. For example there a long thread discussing heirloom seeds and hybrid seeds and how this related to their yields and ability to save seeds. Unless they had posted an earlier comment that revealed whether they were for or against, it was impossible to know whether these people were for or against GM and if they were relating their comments to the GM discussion. That is, just because you may wish to have everyone grow heirloom seeds, doesn’t necessarily mean you are anti-GM. That, at least, was the assumption I chose to make. Other examples included arguments about monoculture V polyculture.
The results
Table 1. Number of comments for each of the two tribes for each category.
| In favour of GM food | Against GM food | Neutral | |||
| Science argument | Science neutral | Values argument | Science argument | Values argument | |
| 29 | 12 | 29 | 9 | 42 | 29 |
The analysis
It is no wonder this debate never moves forward and we keep plodding over the same old ground. From the Table 1, the difference in how the two sides approach the debate is immediately obvious.
The “In favour” camp use science and values equally to argue their case whereas the “Against” camp rely almost exclusively on values. Science barely rates a mention in the “against” camp and if it does it is often based on a flawed understanding of the science, in this case about 50% of the time. Note, however, there were incorrect assumptions from a handful of those arguing in favour of GM crops, though as with the following example, he or she was simply misinformed rather than having a flawed scientific understanding: “Africa would be decimated right now due to massive wheat shortages from the crops being susceptible to bacteria. GM wheat helped revive Africa’s wheat production, staving off a massive food shortage that could have been catastrophic.” I have no idea where this guy would have got this info from.
The majority of the values of those against GM foods alluded to the dislike, mistrust, hate, undesirable ethics of the handful of companies who own the GM crops and the respective patents. This aligns with TechNyou’s experience with the Australian public, as does the breakdown of the comments in general. Other against-based values comments aligned with the “Mother Nature” philosophy and that we are tinkering with things we don’t understand, or that natural is best. The labelling issue (a right to know) and the occasional dose of the yuck factor – ie that it is inherently wrong to put genes from one species into another – were also present.
Risk
It is difficult to extrapolate from my analysis to the general population, but if you took the second values example used above for those in favour of GM foods as a reflection of society as a whole re: this issue, it exemplifies another difference between the tribes and that is our perception of risk. Those in favour of GM foods are less risk averse than those against it. Again. however, this aligns well with the more robust studies out there.
For example, compare the above view with the following comment linked to the Levaux article:
“The insertion of powerful DNA expression promoters and proteins that are very different from those occurring naturally in plants can have dangerous, unintended and unanticipated consequences. Some plants produce toxic chemicals and may even produce harmful proteins or peptides. It is arrogant in the extreme to assume, as you do, that all possible combinations of DNA, proteins and biochemistry is safe for everybody to consume for a lifetime.”
One side is, benefit dependant, prepared to accept some risk, the other side accepts only zero, risk at least when it comes to food. The story is very different if you talk about topics such as medicine.
Venus and Mars
If you want to use a scientific argument, it will more than likely be countered with a values argument, regardless of whether the values are rational or not. Values define a person and they are not about to change them easily. Certainly, attempting to do so with scientific evidence is unlikely to succeed. Conversely, the person who can only see the scientific facts can have trouble understanding the nature of their opponent’s values, though it is notable that the “in favour” camp has an even split between those that used science and values to back their arguments. This is not a criticism of either camp. From where I sit it is human nature and if we are to have such debates move forward then we need to better understand where each group comes from and what makes them tick.
Caveat
Note, as mentioned above this is not a robust analysis. It is my quick, dirty and SUBJECTIVE analysis, so I am sure any worthy social scientist will be able to pick holes in it. However, this analysis does align reasonably well with my personal experience (again anecdotal) and some of the more robust public opinion surveys and peer-reviewed literature.
Substantial equivalence
OK, here is the basics of the arguments put forward about substantial equivalence (SE).
Response from Ari Levaux to critical comments about his position on SE
“I think substantial equivalence is outdated, and Monsanto’s stance against toxicity testing is transparent, arrogant, and reckless. microRNA shows just how much more complicated things are than the assumptions built into substantial equivalence. That said, microRNA provides nothing more than a possible path by which a problem might occur.”
And again
“… Anyway, none of the nitpickers – except the impressively level-headed mirna, have provided any useful response to my points that substantial equivalence is a transparent joke of an unproven hypothesis, and that Monsanto’s stance against toxicity testing is based in business objectives, not scientific objectives.”
My initial thought to Levaux’s response was that his inability to understand and interpret the science (sounds like he didn’t even try) severely dented any credibility to the point that it make it hard to respect his thoughts on substantial equivalence. Nevertheless, the questions of substantial equivalence and the precautionary principle, which he also refers to, are legitimate ones. Whether you agree with Levaux or not is another matter. Levaux claims the objectives are based on business rather than science.
The precautionary principle is equally controversial. I am no expert, but the conversations I have had with people on this topic are steeped more in values and personal ethics than anything to do with science. Much of it comes down to your definition of safe, though that is a bit simplistic. Interpretations of the precautionary principle are as many and varied as those of the bible. This has been the case even as far back as my third year undergrad class 20 years ago when it was part of an assignment and tutorial topic.
Becasue Australia uses substantial equivalence as the basis to assess GM foods, I thought it pertinent to at least present some more details on the issue. Levaux’s arguments can be read in his articles and his responses to the comments. The following details are largely from the dudes at Biofortified
Karl Haro Von Mogel – part of a posted reply to Levaux
…Your treatment of Substantial Equivalence is simplistic and you don’t indicate that you understand precisely what is meant by it, and why it was developed. There is a perception amongst anti-GE individuals that it is some sort of way of avoiding testing, when in fact it is a way to determine if there is a biochemical or nutritional change that falls outside the natural range of variation, which would suggest further testing. It is not an assumption of equivalency, but a determination that is reached only after testing has occurred. It doesn’t preclude further testing, nor is it a claim that there is no possible side effects from genetic engineering. Genes exist in a connected network of activity, and any change, including by mere breeding, can have effects on that system. Substantial equivalence is in fact a recognition of this fact that a genetically engineered trait can significantly affect this system, and if it does, further scrutiny is advised.
Anastasis Bodnar
Bodnar had previously written a reasonably extensive article for Biofortified, though it is written from a US/FDA perspective.
What substantial equivalence can do is give us a starting point.
We know that there is variation in amounts and types of proteins and metabolites, gene expression, and other parameters from variety to variety, from environment to environment, and from plant to plant. For example, if I use a microarray to find similarly and differently expressed genes in two genetically identical plants grown in slightly different environments, such as different temperatures, I will find some genes that have significantly different expression. Similarly, plants of different varieties grown in the same environment will have different gene expression profiles and even two identical plants in the same environment will have some differences.
The first step in a comparative assessment is to test and compare the genetically engineered variety to a genetically similar variety that doesn’t have the trans- or cis-gene. Tests can include gene expression, metabolic profiles, feeding studies, and more. If differences aren’t found in a reasonably wide panel of tests, then the genetically engineered variety can be called substantially equivalent to the genetically similar variety. More here…
Finally, the perspective of the Australian Regulator, Food Standards Autralia New Zealand (FSANZ)
Backyard Biotech and the rise of the Biohacker
By Jason Major
Technyou
There is a large, active and vibrant community of backyard biotechnologists out there and, until recently, I had no idea they existed. Known as ‘Biohackers’, this group of citizen scientists could be a creative resource, but do they also represent a risk, even if a negligible one at this stage?
Some of these guys tinker with biological parts such as genes to create novel biological systems, potentially novel life with the tools used for synthetic biology, though most are doing nothing more harmful than DNA extraction. But the ability to get into the risky stuff could become easier as equipment costs continue to plummet, our understanding of genetics increases and the plug and play genetic parts available already get a bit more sophisticated.
Escape
The risk is the potential for these novel organisms to escape from the lab (or garage, kitchen…), either accidentally or by those with more nefarious intentions. This raises the question of how and if we should monitor and regulate such activity? You want to avoid suppressing the potential creativity and freedom of this activity yet prevent the nutters out there from expressing their own version of freedom?
Come into my lab, and see what’s on the slab
My ignorance of the extent of biohacking is embarrassing, though it is hard to ascertain how many in these groups are actually doing science and how many are just joining in the conversation. Even so, I was astounded at the complexity of some of the research being done and equipment readily available and accessible to anyone with the inclination. I’m not talking simple chemical sets and kitchen chemistry such as DNA extractions; I mean proper gene sequencing, gene transformation and synthetic biology. They make everything from bioluminescent yogurt to arsenic biodetectors.
One self proclaimed biohacker, Meredith Patterson is conducting experiments in her kitchen on a budget of less than $200. She is attempting to transform yogurt bacteria to signal the presence of melamine, the toxic stuff found in dairy products in China a couple of years ago.
Pocket money
To give you an indication of the rapid changes, when I did my undergrad between 1987 and 1989 the cost of a standard gel electrophoresis kit was such that we were only allowed to watch the lecturer operate it in case we broke it, which we probably would have. Nowadays you can buy them from toy shops and many high schools have them. Even the cost of sequencing DNA is plummeting. The DNA synthesizing machine is what you will need to make your DNA strands, which could be genes or bits of RNA that control how your genes work. You can get a small or older model DNA synthesizer on e-Bay for less than $1000. PCR machines (your DNA photocopier) can be even cheaper. Or you can simply bypass this step. For a few cents per nucleotide, there are companies that will synthesize your genes or DNA sequences for you and ship them to you anywhere in the world. You can pick up a centrifuge for about $50 that hooks up to your drill. A lot of chemical supplies are easily bought online or local supplier and in Australia, at least, there are companies that sell small quantities for schools and people like me. Live in a shoebox? No problem, there are organisations that rent out lab space with all the machines that go bing that specifically target themselves to biohackers.
There is even an iPhone app to check the compatibility of chemicals so you don’t burn down or blow up your garage or worse, your Mum’s kitchen.
Given a kid with an after school job and some pocket money could quickly save enough to set up a basic operation, this sort of science is no longer just the domain of those with well-funded university or industry laboratories. Nor do you require a PhD or similar educational background. The how to bit is easily sourced from an extensive network of support groups all just a mouse click away.
Some chemicals and equipment, of course are hard to get and far from cheap, but like any hobby, it depends on how far you want to take it. Cycling, scuba diving, all these hobbies of mine could easily cost me 10s of thousands if I became like some of the gear freaks I have knocked around with. I am unsure, but I am also guessing that there would be certain chemicals and equipment that should you manage to purchase them or even attempt to, would raise flags with certain authorities.
Getting inspiration
One large support network that appears to be actively encouraging the biohacker network is the International Genetically Engineered Machine Foundation (iGEM) which is an open, community-based organisation dedicated to education in this scientific field. Each year they run a synthetic biology competition originally available only to undergraduate students through their universities, but last year they introduced a category for high school and this year there is an entrepreneurial category.
Teams are given a kit of biological parts from the Registry of Standard Biological Parts to use, plus whatever genetic parts they have designed themselves to build their own biological system and operate them in living cells. this is where you get those plug and play parts, I mentioned. This registry is where you get those plug-and-play genetic parts I mentioned above. These parts include genes, gene promoters, etc that have universal bits of DNA on the end to allow you to plug any part together like LEGO.
Regulation
Now that we can (sort of) create synthetic life in our lab – backyard version or otherwise – how do we make sure it stays there, or that it is used responsibly? Is this even possible? No technology, in fact nothing full stop is risk free. Synthetic biology, however, does result in living things that have the potential to breed, though bacteria divide rather than breed.
For now, our limited knowledge means that anything produced in a nice controlled lab environment will be unlikely to survive in the harsh and dog-eat-dog natural world. And access to dangerous viral agents or their genetic sequences is restricted. Technically, you could get the necessary genetic bits for a virus and stitch them together, but that really does requires a sophistication beyond the backyarders, even most well-funded research labs, largely because of the level of containment required to prevent infecting yourself. But how long can this low risk environment last? Knowledge in this field is proceeding at a rapid pace.
I doubt such a group could self regulate so I dare say big brother will have a hand in this somewhere. Likely there will also need to be some form of voluntary code of conduct and self-policing, which many groups are already advocating and developing alongside regulatory agencies, research labs and other organisations such as the Woodrow Wilson Center’s Synthetic Biology Project.
The crash of the ivory tower
If nothing else, this sort of DIY science strips out the elitism surrounding this area of science and makes it accessible to the public. It may help ignite interest, excitement and understanding about science that no text book or lecture can. Suppression of this via over-regulation should be avoided. One thing for the biohackers to consider is the term biohacker. Personally, it conjures up images of nefarious dudes in dim garages plotting to destroy the world. Does anyone have a better term?
Who are these biohackers?
There is no shortage of groups and expertise to tap into, all readily available via the myriad social media networks and Internet. This short list will get you links to most of the groups and individuals operating in this space
Biocurious: “… a nonprofit community lab, education facility, and “hackerspace” for biotechnology hobbyists and professionals.”
DIY Bio: “…dedicated to making biology an accessible pursuit for citizen scientists, amateur biologists and biological engineers who value openness and safety.”
Garage Bio: “…a podcast devoted to cheap and DIY approaches to biology. The goal is to make academic and industry advances understandable to an amateur audience and promote a spirit of scientific discovery and fun exploration.”
Update
I just found that Australia’s Office of the Gene Technology Regulator (OGTR) has at least recognised that biohacking exists
More info
Nature Biotechnology Biotech in the basement December 2009 Vol 27 (12) pp 1077-1078
First primate chimeric offspring produced
The first successful birth of monkeys developed from stem cells taken from two separate embryos.
Science Daily: 5 January 2012
TechNyou
Note that this research provides significant new information about how early embryonic stem cells develop and take part in formation of the primate species. There is no intention of creating chimeric humans. Even if some scientist did want to do it, it would never (one would hope) get past the gauntlet of ethics committees.
Homepage Image: Oregon Health and Science University
Assessment of long-term, multigen feeding studies says GM foods are safe
Jason Major
TechNyou
A review of long-term and multi-generational animal feeding studies declares GM foods are safe, though there are many criticisms of the studies.
The review appears in the journal Food and Chemical Toxicology (in press). They analysed 12 long-term (greater than 90 days) feeding trials and 12 multi-generational feeding trial on a range of GM crops and traits. They analysed these alongside the many 90 day or less feeding studies.
Their overall conclusion is that GM plants are nutritionally equivalent to their non-GM counterparts and can be safely used in food and feed. The caveat here is that the reviewers had serious concerns with the study design and consequent strength of the statistical analysis for a lot of the studies reviewed. Topping the concern list was the lack of a comparable isogenic lines in the feeding trials. This means that the GM cultivar the researchers used was different to the non-GM one they used as a control. For example, if you go to the nursery to buy sweet corn, you will have loads of different varieties to choose from – all different cultivars. Each of these varieties (or cultivars) will have different nutritional and metabolomic/proteomic, etc profiles and consequently your body will produce different metabolites, etc in response to them. Hence if you have a specific GM cultivar, you should use the same cultivar without the transgenic trait for an accurate comparison.
There were also concerns with many trial having insufficient animals to provide sufficient statistical strength – the more you have the more certain you can be about your results.
Statistics V Biology
One thing that needs to be pointed out is that there is a big difference between something that is statistically significant and something that is biologically significant. In a few of the studies some parameters showed small differences that were statistically significant but not biologically significant. In the case of toxicology, it is the biologically significant that is important. For example, if 10 units of a particular toxin found naturally in a food is declared harmless for humans, and the normal range in a specific cultivar or plant is between 2 and 5 units. If your GM plant is found to have 6 units that may be declared statistically significant, but it is still going to be harmless from a biological perspective so has no biological significance and would be considered safe to eat.
It will be interesting to see if there is any controversy of this review. I have yet to see any which is surprising given the amount of uncertainty regarding the scientific methodology on some of the public papers and the criticism from the review authors. I would have thought this would have provided loads of ammunition for the opposing camps in this debate. Maybe it is too close to Christmas?
Can GM-free biofortified crops succeed after Golden Rice controversy?
Howarth Bouis from HarvestPlus explains why their non-GM biofortified crops with higher portions of key vitamins can succeed in tackling malnutrition.
The Ecologist: 12 December 2011
TechNyou
This gives an insight into the issues of micro-nutrient deficiency worldwide. However, Bouis implies that HarvestPlus focus only on non-GM breeding technologies to develop biofortified crops. HarvestPlus fund the University of Melbourne research being done by Dr Alex Johnson to develop iron-enriched rice using transgenic (GM) technologies.
And some TechNyou commentary on the Golden Rice V Iron-enriched rice
Xenotransplantation: using pigs as organ and tissue donors for humans
Transplantation is the best available treatment for serious health problems such as diabetes, kidney failure and heart disease. Can pigs be our donors?