Researchers in Kobe, Japan and Boston have made the biggest breakthrough in stem cells yet, producing "embryonic-like" stem cells from mice by exposing differentiated cells to the stress of an acid bath. Previous methods of producing embryonic stem cells required complex genetic engineering or tedious cell sorting. This new technique simply involves bathing blood cells in a weakly acidic solution for half an hour.
The result was so surprisingly that at researcher who discovered it, the young Haruko Obokata at the Riken Institute for Developmental Biology in Kobe, didn't believe it at first. Neither did her colleagues. “I was really surprised the first time I saw [the stem cells]… Everyone said it was an artifact – there were some really hard days,” Dr. Obokata said. The new cells have been dubbed STAP cells by the researchers.
Proposals involving embryonic stem cells are one of the basic building blocks of the field of regenerative medicine. The cells made by Dr. Obakata were shown to be capable of differentiating into dozens of specialized cells, from cardiac-muscle cells to nerve cells. Though the results were obtained with mice, it experiments with human cells are already underway and may already be successful.
A simple and cheap process to produce embryo-like stem cells from blood cells rather than human embryos leapfrogs most of the ethical qualms which made these cells such a focus of controversy in the early 2000s. Prominent Republicans such as John McCain have already come forward in favor of stem cell research.
This stem cell breakthrough is so huge because of its ease. The process is so simple that it can be carried out in a lab without any special knowledge or equipment. It seems likely that the process will be duplicated in DIY garage bio-labs across the country. With the technique becoming so easy, regulation or ethical restriction becomes much more difficult, if not completely impossible.
Experts foresee embryonic stem cells being used to manufacture replacement organs and tissue for use in regenerative medicine therapy. Livers have already been grown from mouse stem cells. Scientists have already made lab-grown tear ducts, windpipes, and arteries. Dr. Obokata said that finding will open possibilities in "the study of cell senescence [aging] and cancer as well. "
Imagine a world where people can be saved from what are currently fatal heart attacks by receiving a transplanted heart grown from their own stem cells. With this game-changing advance, that world might not be far off.
(PhysOrg.com) -- Biomedical researchers at the University at Buffalo have engineered adult stem cells that scientists can grow continuously in culture, a discovery that could speed development of cost-effective treatments for diseases including heart disease, diabetes, immune disorders and neurodegenerative diseases.
UB scientists created the new cell lines - named "MSC Universal" - by genetically altering mesenchymal stem cells, which are found in bone marrow and can differentiate into cell types including bone, cartilage, muscle, fat, and beta-pancreatic islet cells.
The researchers say the breakthrough overcomes a frustrating barrier to progress in the field of regenerative medicine: The difficulty of growing adult stem cells for clinical applications.
Because mesenchymal stem cells have a limited life span in laboratory cultures, scientists and doctors who use the cells in research and treatments must continuously obtain fresh samples from bone marrow donors, a process both expensive and time-consuming. In addition, mesenchymal stem cells from different donors can vary in performance.
The cells that UB researchers modified show no signs of aging in culture, but otherwise appear to function as regular mesenchymal stem cells do - including by conferring therapeutic benefits in an animal study of heart disease. Despite their propensity to proliferate in the laboratory, MSC-Universal cells did not form tumors in animal testing.
In the comments, Martin said:
I wonder how accurate it is. Uncle Fester became underground famous in the 90s when he published books on meth and acid manufacture, but other clandestine chemists criticized his syntheses for being inaccurate.
From this small snippet, it sounds like he wants you to go out and find the right Clostridium species and strains in soil and culture them yourself, which sounds as impractical as his suggestion in the acid book to grow acres of ergot-infested rye. :)
Any more comments on why this is impractical? It sounds much simpler than growing acres of ergot-infested rye. He describes how he would isolate spores, first by heating the culture (this kills anything that is not a spore), then encouraging growth in an anoxic environment (kills anything that is not anaerobic). This leaves only anaerobic bacteria derived from spores.
The book does claim that botulinum germs are "fussy about what they like to grow in, its pH, and its temperature" and that "This need to exclude air from the environment where the germs are growing is the most difficult engineering challenge to the aspiring cultivator of Clostridia botulinum", so he's not saying that it's a cakewalk.
Of course, many of these underground books (Anarchist Cookbook...) are rife with misinformation. Anyone serious about producing botulism toxin would need actual biochemical knowledge and multiple corroborating sources. Still, there's a lot of information in this particular book that would at least provide a compelling starting point.
It's worth noting that Uncle Fester probably never synthesized all the compounds described in his book, which includes over half a dozen different types of nerve gas. He repeatedly points out that synthesizing these chemicals is a risk to the life of the person performing the synthesis. In some parts of the book, he names sources, like literature released by the military, but the vast majority of his book lacks citations.
A minor personal announcement -- I've been hired to work half-time for Halcyon Molecular in Redwood City. I'm mostly going to be working on improving their website content. Halcyon was founded by Michael and William Andregg, who I originally met in Tucson at a Center for Responsible Nanotechnology conference in 2007.
Halcyon is developing a technology to sequence genetic material at orders of magnitude faster than anything on the market or in the pipeline. Their technology and approach, which uses electron microscopy, is really unique. I'm happy I finally get to talk about the company and technology a bit in public because I've been excited about them in private for a long time.
Also keep in mind that Halcyon is actively looking for new researchers.
From The Wall Street Journal:
Rapid advances in bioscience are raising alarms among terrorism experts that amateur scientists will soon be able to gin up deadly pathogens for nefarious uses.
Fears of bioterror have been on the rise since the Sept. 11, 2001, attacks, stoking tens of billions of dollars of government spending on defenses, and the White House and Congress continue to push for new measures.
But the fear of a mass-casualty terrorist attack using bioweapons has always been tempered by a single fact: Of the scores of plots uncovered during the past decade, none have featured biological weapons. Indeed, many experts doubt terrorists even have the technical capability to acquire and weaponize deadly bugs.
The new fear, though, is that scientific advances that enable amateur scientists to carry out once-exotic experiments, such as DNA cloning, could be put to criminal use. Many well-known figures are sounding the alarm over the revolution in biological science, which amounts to a proliferation of know-howâ€”if not the actual pathogens.
Another bit later in the article:
All the government attention comes despite the absence of known terrorist plots involving biological weapons. According to U.S. counterterrorism officials, al Qaeda last actively tried to work with bioweapons--specifically anthrax--before the 2001 invasion of that uprooted its leadership from Afghanistan.
This is great. It's best to pay attention to obvious risks, like this, nuclear terrorism, the integrity of the power grid under solar storms, major earthquakes, etc., before they happen, not after. Often times, adequate preparation even requires little marginal effort.
Gladstone scientists discover new method for regenerating heart muscle by direct reprogramming
Next-generation reprogramming of native cells offers therapeutic advantages
Scientists at the Gladstone Institute of Cardiovascular Disease (GICD) have found a new way to make beating heart cells from the body's own cells that could help regenerate damaged hearts. Over 5 million Americans suffer from heart failure because the heart has virtually no ability to repair itself after a heart attack. Only 2,000 hearts become available for heart transplant annually in the United States, leaving limited therapeutic options for the remaining millions. In research published in the current issue of Cell, scientists in the laboratory of GICD director Deepak Srivastava, MD, directly reprogrammed structural cells called fibroblasts in the heart to become beating heart cells called cardiomyocytes. In doing so, they also found the first evidence that unrelated adult cells can be reprogrammed from one cell type to another without having to go all the way back to a stem cell state.
The researchers, led by Masaki Ieda, MD, PhD, started off with 14 genetic factors important for formation of the heart and found that together they could reprogram fibroblasts into cardiomyocyte-like cells. Remarkably, a combination of just three of the factors (Gata4, Mef2c, and Tbx5) was enough to efficiently convert fibroblasts into cells that could beat like cardiomyocytes and turned on most of the same genes expressed in cardiomyocytes. When transplanted into mouse hearts 1 day after the three factors were introduced, fibroblasts turned into cardiomyocyte-like cells within the beating heart.
"Scientists have tried for 20 years to convert nonmuscle cells into heart muscle, but it turns out we just needed the right combination of genes at the right dose," said Dr. Ieda.
Great article from h+ magazine from about a week ago: "Rethinking the Promise of Genomics". This is by Terry Grossman, co-author (with Ray Kurzweil) of Fantastic Voyage:
I used to be a big believer in the enormous potential of genomics, and each of my two previous books, Fantastic Voyage and TRANSCEND: Nine Steps to Living Well Forever, had chapters devoted to this topic. The relevant chapter in the earlier book, Fantastic Voyage, published in 2004, was titled "The Promise of Genomics." My co-author in these books, Ray Kurzweil, is widely regarded as one of the world's foremost inventors and futurists, and he has made predictions for what is likely to occur in the future in the field of genomics . Yet, these days I find that I am feeling far less confident at least for the near term about the near term prospects for this "promise."
Here's a key quote by Grossman:
Currently I have moved much closer to the idea of "genetic irrelevance," the idea that in the overwhelming majority of cases, our genes are of much less importance in determining our fate and that the environment in which we live and the lifestyle choices we make are of far greater importance.
Please note that I said this is true in the "overwhelming majority of cases," but it is not true all the time. About one in 20 people is born with an abnormal gene that will create a major problem that can affect life and be quite relevant, either from birth or at some point further down the line. Examples include cystic fibrosis, a genetic disease that can manifest from birth for which we have been doing routine screening for decades and the BRCA-1 and BRCA-2 genes, which dramatically increase a woman's risk of breast and ovarian cancer later in life. But for nearly 95 percent of us, we come off of the assembly line of birth virtually perfect.
Illuminating stuff. Go exercise! It's important that the advocates of science and technology make it clear to the public that we are willing to be pessimistic about a technology's dividends when it looks rational to do so. Grossman's article reminds me of an excellent 2001 article by John Smart, "Performance Limitations on Natural and Engineered Biological Systems":
The more complex any life form becomes, the more it becomes a legacy/path dependent system, with many antagonistic pleiotropies (negative effects in other places and functions in the organism) whenever any further change is contemplated. It seems that evolutionary development, just like differentiation from a zygote or stem cell to a mature tissue, becomes increasingly terminally differentiated the more complex and specialized the organism. One extreme case of this kind of terminal differentiation, at the cellular level, is nerve cells in the human brain, which are so specialized, and the connections they support so complex, that they cannot even replace themselves, in general. Could they eventually learn to do so without disrupting the connectionist complexity that they create in the brain, after their development has stopped? Perhaps not. The more complex the system becomes, the less flexible it is. It gets progressively harder to make small changes in the genes that would improve system, and given how finely tuned so many system elements are, large changes are out of the question.
Because the reasons outlined by Grossman and Smart, I am more in the school that cybernetics (implants, brain-computer interfaces, wearable computing, etc.) will provide the most significant performance upgrades to humans in the nearer term (20-30 years). At first bio-transhumanism will be more of a side phenomenon than the central thrust of the transition. There will be much more effective and reliable means to make humans stronger and faster before we can make ourselves live longer and deeply exploit our own genetics.
From the Genetic Archaeology blog:
Humanity's physical design flaws have long been apparent - we have a blind spot in our vision, for instance, and insufficient room for wisdom teeth - but do the imperfections extend to the genetic level?
In his new book, Inside the Human Genome, John Avise examines why - from the perspectives of biochemistry and molecular genetics - flaws exist in the biological world. He explores the many deficiencies of human DNA while recapping recent findings about the human genome.
Distinguished Professor of ecology & evolutionary biology at UC Irvine, Avise also makes the case that overwhelming scientific evidence of genomic defects provides a compelling counterargument to intelligent design.
Here, Avise discusses human imperfection, the importance of understanding our flaws, and why he believes theologians should embrace evolutionary science.
Our brains and bodies are both full of flaws. According to the pre-transhumanist worldview, the plan is just to sit around for the rest of eternity with these flaws, even as we colonize the Galaxy. According to the transhumanist worldview, the plan is to analyze these flaws, debate whether they are flaws or not, and consider fixing them if it seems practical and desirable. The latter makes sense, the former doesn't.
The New Scientist CultureLab blog has more info on the book.
From yesterday's list of links, I particularly want to call attention to the rotifer link. This press release is interesting because it shows how animals can survive even when they are exact genetic copies of one another. Instead of outcompeting parasites through mutation, they run away by going into cryptobiosis. I predict that a form of asexual multicellular synthetic life will be created by 2030 that can defend against parasites through aggressive defense, say silica spines, so that running away isn't even necessary. These organisms will just sit around and reproduce. The primary method to get rid of them at first will be dessication, but this will eventually prove useless as they disperse too widely to target.
What many humans don't realize is that we are surrounded by quintillions of organisms with very little genetic diversity that dominate us in terms of biomass and persistence. They are the status quo -- we are the aberration. These are organisms that have survived every mass extinction. Culprits include the tardigrades (which can survive outer space), nematodes (absolutely ubiquitous; it is estimated there are between 1018 (one quintillion) and 1021 (one sextillion) nematodes worldwide, and they are crawling all over you right now), chaetognaths (considered useful models of basal bilaterans, there are a lot of them in the oceans, really a lot), and so on.
The only reason that these organisms aren't ripping us all to shreds right now is because there have been no synthetic biologists to push them out of evolutionary minima and give them more sensible strategies for total domination. Sorry to be alarmist, but I studied evolutionary biology for a couple years and that is my opinion. Evolution is terribly poor at transversing local minima to reach a global optima, and that is really the only saving grace for fragile macroscale multicellular agglomerations like ourselves. Interesting and low-energy-cost evolutionary innovations are rarely combined because they require several working parts to come together which are maladaptive individually but adaptive in cooperation.
The reason why rotifers are interesting is that their lack of genetic diversity makes them a good model for self-replicating machines. The ability to switch into a dormant, armored state (cryptobiosis) seems characteristic of a variety of small organisms, and we can expect this ability to be exploited to the fullest by human-engineered microscale replicators. The ability to distribute many of these replicators across a wide area will eventually create a "viral load" scenario analogous to the one faced by aging humans -- so many diverse beings build up in our body that the workload faced the immune system to combat nascent infections eventually becomes prohibitive and the system breaks down.
Some scientists have laughed at the idea that human-engineered organisms could dominate microbes that have evolved for billions of years, but I find this ridiculous. Human-engineered artifacts have already outperformed everything created by evolution in terms of energy density, speed, mass, acceleration, local dominance, and so on. The key point is that evolution is radically dumb (but it has many trials available) and humans are very smart. Let's discuss some of the ways to engineer microorganisms that cannot be defeated by the legacy biota.
1. Broad-spectrum biocides: natural organisms use a variety of biocides, but observe that humans have created thousands of highly effective synthetic antibiotics and biocides that evolution never discovered even after four billion years of experimentation.
2. Phage-immune bacteria, for instance bacteria that use genetic programs incompatible with malicious code injection by phages. Phages are the main bacteria-curtailing force on the planet and we depend on them for our survival.
3. Bacteria specifically engineered for immunity to broad-spectrum antibiotics which produce and secrete these antibiotics as a biofilm. There is even the possibility of release-and-shield, where microbes release the biocide then shield themselves from it for long enough for the competitors to be defeated, at which point the shield is raised.
4. Sucking them in: microorganisms could coat themselves in a gel shield which absorbs and dissolves both nutrients, phages, and rival microbes. For instance, the extracellular matrix of animal tissues is much stronger than the slime layer used by bacteria. Cooperative colonial bacteria could create stronger extracellular shields depending on how well-established the colonial region is, devoting stronger shields to the colonial center and weaker shields to the exploratory fringes.
5. Incubation-then-release: many evolutionary minima involve colonial organisms that are evolutionarily strong in larger colonies but evolutionarily weak in small colonies. By sterilizing a large area, filling it with nutrients, and allowing a founder population to develop (a "mega petri dish"), an important evolutionary minima could be hopped.
6. Quorum computing: evolution has developed a variety of means for microbes to communicate with one another on a crude level: quorum sensing. One of the interesting evolutionary innovations of the last billion years was to produce multicellular organisms that survive against many uncooperative microbes. By creating microbial superorganisms that effectively cooperate and compute using biocomputation, it may be possible to beat multicellular life at its own game by creating "organisms" miles across that effectively cooperate to defeat all rivals. This is definitely not a near-term risk but it could be a risk within the lifetimes of many alive today, given no singleton that guards us at a low level.
7. The last point in particular opens up a very large space for experimentation. For a colony that knows how to differentiate its perimeter members from interior members, it can activate all sorts of interesting genes in the perimeter members to make life miserable for organisms next to them. Bacteria already do this in a rudimentary way with quorum sensing. As long as a suitable barrier can be erected, the production of a variety of poisons is possible and safe for the majority of the colony.
Even natural selection in hospitals is enough to create killer bacteria immune to many antibiotics. What about bacteria specifically engineered by smart humans for reproduction and survival?
George Dvorsky at Sentient Developments points us to an op-ed at New Scientist titled "Fears over 'designer' babies leave children suffering". The author writes:
Such fears are misplaced: IVF-PGD is little use for creating designer babies. You cannot select for traits the parents don't have, and the scope for choosing specific traits is very limited. What IVF-PGD is good for is ensuring children do not end up with disastrous genetic disorders.
I, along with dozens of prominent scientists in the field, disagree -- IVF-PGD would be useful for creating designer babies. Would would would. To boost this position, the author links another New Scientist article... (one that he probably edited, being biology features editor) which seems to contradict him:
Part of the problem is that only one or two cells are available for screening. Until recently this greatly restricted the tests that could be done. However, new ways of amplifying DNA are making it possible to do hundreds of tests. That means clinics will be able to screen for a much wider range of harmful mutations - and for desirable variants too.
Only one paragraph that I can find appears to support the op-ed author's idea that IVF-PGD couldn't be used for designer babies:
How much further can selection go? What of that object of tabloid hysteria, the "designer baby"? Will we one day be able to ask for a tall, musical, blue-eyed boy or a dark-haired girl? Even if regulatory authorities allow us to use PGD to select desirable gene variants, there are major snags. For starters, IVF typically generates fewer than 10 embryos per cycle. This means parental choice will be very limited. "I don't think anyone in their right mind would ever go through IVF to select the hair colour of their offspring," says Yuri Verlinsky of the Reproductive Genetics Institute, Chicago, one of the pioneers of PGD.
This Verlinsky quote is really confusing. Elsewhere, Verlinsky has been quoted as saying that PGD-IVF could lead to a "disease-free society" (a sloppy way of saying a "genetic disease free society"), but he claims that people won't use it to choose the hair color of their offspring. His quote doesn't make it clear whether he's talking about his opinion or the technical challenge. Also, the author of that (non op-ed) piece seriously breaks journalistic neutrality by calling designer babies an "object of tabloid hysteria" when many prominent scientists in IVF take the idea seriously. It's like the contributors at New Scientist are on misguided vigilante missions to make emerging technologies sound more palatable to the mainstream.
In any case, the limitation on the number of blastocysts can be circumvented using multi-generational in vitro embryo selection, which Verlinsky should have already considered, and if he hasn't, he has tunnel vision. So he either 1) is scientifically uncreative in his own field, or 2) knows that more advanced PGD-IVF could be used for designer babies, and just wants to keep it a secret from the public because he wants to get them to accept the technology incrementally, like boiling a crab in water that increases in temperature only slowly.
In general, I think the op-ed is a shoddy example of memetic engineering -- the author is trying to distract attention away from the designer baby controversy to help promote PGD-IVF for eliminating genetic diseases. Good motive, but somewhat dishonest, because I doubt that even the author believes that PGD-IVF would be useless for designer babies.
Speaking of "designer babies", I hate the term. As James Hughes said in WIRED, "the term "designer babies" is an insult to parents, because it basically says parents don't have their kids' best interests at heart". How about just "PGD-IVF babies", a non-catchy term, because it shouldn't become catchy and be used to discriminate against children born using the tech or parents who decide to use it? This would be in the same vein of Aubrey calling his project "Strategies for Engineered Negligible Senescence" to make it deliberately difficult to misunderstand. The project of SIAI could become, "the Engineering of a Human-Values Reflective Optimizing Process".
Either way, the whole issue matters not, because designer babies are largely irrelevant and will be eclipsed by things like strongly self-improving superintelligence and molecular manufacturing. See "Evolution by Choice" by Mitchell Howe.
BERKELEY, CA â€“ Scientists at the U.S. Department of Energy's Lawrence Berkeley National Laboratory can now control how cells connect with one another in vitro and assemble themselves into three-dimensional, multicellular microtissues. The researchers demonstrated their method by constructing a tailor-made artificial cell-signaling system, analogous to natural cell systems that communicate via growth factors.
Artificial tissues are presently used in medicine for a range of applications such as skin grafts, bone marrow transplants, or blood substitutes, as well as in basic medical and biological research. Tissue engineers try to improve upon or repair natural tissues by manipulating living cells from one or more donors, sometimes in combination with synthetic materials. Unfortunately, in this "top down" approach, the cells assemble themselves randomly, losing the 3-D organization that is key to many tissue functions.
"Our method allows the assembly of multicellular structures from the 'bottom up,'" says Carolyn Bertozzi, principal investigator in the research, who directs DOE's Molecular Foundry nanoscience research facility at Berkeley Lab and is a member of the Lab's Materials Sciences and Physical Biosciences Divisions. "In other words, we can control the neighbors of each individual cell in a mixed population. By this method, it may be possible to assemble tissues with more sophisticated properties."
Bottom-up cellular manufacturing -- available now! Next -- molecular manufacturing using specialized organelles that extrude inorganic materials. Superlative futures, here we come!
A proposed name for the new kingdom of synthetic life: Anthropobiota.
(This is hardly original... see Anthropocene, but it seems most likely to catch on.)
The first member of Anthropobiota will likely be Mycoplasma laboratorium, at the J. Craig Venter Institute. The group also "hopes to eventually synthesize bacteria to manufacture hydrogen and biofuels, and also to absorb carbon dioxide and other greenhouse gases", according to the Wikipedia page. This would lead to additional species for specific purposes. The point of Mycoplasma laboratorium is to implement a "minimal bacterial genome", a jumping-off point for future synthetic species. All of these species would fall under Anthropobiota, as long as the genetic material is entirely synthetic. If not, that's just genetic engineering.
Anthropobiota would be located outside the root of the Tree of Life. It would be a complementary Tree, at first much smaller than the original. The Tree of Life contains between 10 million and 1 billion bacteria species, between 10 and 30 million animal species, and some unknown quantity of archaea. So quite a few new species would need to join Anthropobiota for it to rival the current Tree.
I seem to remember an accusation in some phylogenetics journal that a group of Archaea was outside the root of the Tree of Life, but I can't find it for the life of me. Anyway, there could be two or more separate Trees of Life. Anthropobiota will be a new one. The Tree of Synthetic Life.
Two different species within Anthropobiota need not evolve from other species in the same group. Each one could be created from scratch, by scientists in a lab. Once we develop the technology to reliably and inexpensively synthesize long genomes from nucleic acid precursors, and swap them for native genomes, we're in business. The flood gates for new species -- both benign and malign -- will open.
The Lifeboat Foundation A-Prize page is a foresightful effort to to put development of artificial life forms in the open, where it should be. It a reward to whoever creates the first life form that "must execute at least one synthetic nonbiological operation in order to complete its life cycle".
On the A-Prize page, Dr. Alan H. Goldstein, Professor of Biomaterials at Alfred University, creates four classifications of life: Natural Biological, Genetically-Engineered Biological, Synthetic Biological, and Synthetic Nonbiological (Animat). According to his classification system, Mycoplasma laboratorium would fall into the third category: Synthetic Biological. It will not be eligible to collect the A-Prize, because that would require an organism that integrates an entirely nonbiological, consistent (over generation) element into its biological life cycle.
Anyway, I'm looking forward to the creation of Mycoplasma laboratorium later this year. I hope that creating synthetic life stays expensive for at least a couple more decades.