2014Marek Vácha

3rd Faculty of Medicine UK, Prague

Building a better mouse

In 1982 Ralph Brinster and Richard Palmiter created "transgenic" animals by inserting a rat gene for growth hormone into mouse embryos. The mice that carried the new gene, like the one shown here on the left, produced growth hormone and grew twice as big as their normal siblings.

Brinster, School of Veterinary Medicine, University of Pennsylvania

GFP

Green generation

Taiwan: DNA from jellyfish was added to about 265 pig embryos which were implanted in eight different sows.

Four of the female pigs became pregnant and three male piglets were born

The pigs are transgenic, created by adding genetic material from jellyfish into a normal pig embryo.

Green generation

They are the only ones that are green from the inside out. Even their heart and internal organs are green

It remains to be seen, whether from the ethical point of view… ….everything is ok?

ANDi

ANDi

a transgenic rhesus monkey has been born that carries the gene for green fluorescent protein (GFP) in each cell of his body

the gene for GFP was inserted into a viral vector that was injected into the space between the oocyte and the zona pellucida in a rhesus monkey egg.

The vector inserted the GFP gene into the egg DNA, and the resulting offspring, a monkey called ANDi (=inserted DNA) has GFP genes in all of his cells

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer Associates, Inc. W.H. Freeman & comp. Sunderland, MA U.S.A. p. 196)

Frankenfish

Frankenfish

The GM Atlantic salmon grows twice as fast as its wild cousin.

Its genes have been artificially augmented with DNA taken from two other fish – the Pacific Chinook salmon and an eel-like species called an ocean pout

(Zoarces americanus) – in order to boost the growth hormone that allows it continually to put on weight throughout the year.

http://www.independent.co.uk/news/science/a-giant-leap-into-the-unknown-gm-salmon-that-grows-and-grows-2085856.html

The Enviropig

A genetically engineered pig recently approved for limited production in Canada makes urine and feces that contain up to 65 percent less phosphorous, officials have announced.

The Enviropig

Between 50% and 75% of the phosphorus present in cereal grains including corn, soybeans, barley and wheat is present in an indigestible compound called phytate that passes through the pig's digestive tract. The Enviropig is a genetically enhanced line of Yorkshire pigs with the capability of digesting plant phosphorus more efficiently than conventional Yorkshire pigs.

Source: University of Guelph

That could be good news for lakes, rivers, and ocean deltas, where phosphorous from animal waste can play a role in causing algal blooms. These outbursts of algae rapidly deplete the water's oxygen, creating vast dead zones for fish and other aquatic life.

Swine in the United States primarily eat corn, while those in Canada munch on cereal grains, including barley. But the kind of phosphorus that occurs naturally in those plants is indigestible without an enzyme called phytase, which pigs lack.

Most farmers feed their pigs this enzyme as a supplement. But ingested phytase isn't as effective at breaking down phosphorus as phytase created inside the pig would be, so a fair amount of the element gets flushed out in pig waste. That waste, in turn, can make its way into the water supply.

To make sure the modification would work in mammals, the team paired the E. coli genes with a mouse DNA promoter, a section of DNA that encourages replication of a specific segment—in this case the bacterial genes. Researchers then injected microscopic fertilized pig embryos with the mixture.

Early trials revealed that the bacterial enzyme was not only incorporated into the pig genome, it could be inherited by the genetically engineered pigs' offspring.

"We are now in the eighth generation of pigs, and it has been transmitted to all of those generations," said Cecil Forsberg, a University of Guelph microbiologist and lead researcher on the project.

"And from our testing, there is no change in the structure of the gene throughout those generations."

With the added genes, Enviropig is able to absorb more phosphorous from its feed, so less of the element ends up unused and excreted.

The Enviropig

Each one contains genes from mice and E.coli bacteria, which have been inserted into their DNA with absolute precision.

Those genes make a small but important difference to the way these pigs process their food.

Ordinarily, pigs cannot easily digest chemicals called phosphates. That means that the stuff that comes out of the back end can be toxic and damaging to the environment. The phosphates are easily washed into waterways, where they can produce a hugely fertile environment for plants. But the plants grow so rapidly that they choke the stream or river and cause huge damage to the ecosystem.

The genetic modification enables these pigs to digest phosphates, which means they are less polluting and cheaper to feed.

http://www.bbc.co.uk/news/world-us-canada-12113859

Fluorescent mice

GloFish

In 2007, South Korean scientists altered a cat’s DNA to make it glow in the dark and then took that DNA and cloned other cats from it — creating a set of fluffy, fluorescent felines. Here’s how they did it: The researchers took skin cells from Turkish Angora female cats and used a virus to insert genetic instructions for making red fluorescent protein. Then they put the gene-altered nuclei into the eggs for cloning, and the cloned embryos were implanted back into the donor cats — making the cats the surrogate mothers for their own clones.

Scientists at the University of Washington areengineering poplar trees that can clean up contamination sites by absorbing groundwater pollutants through their roots. The plants then break the pollutants down into harmless byproducts that are incorporated into their roots, stems and leaves or released into the air. In laboratory tests, the transgenic plants are able to remove as much as 91 percent of trichloroethylene — the most common groundwater contaminant at U.S. Superfund sites — out of a liquid solution. Regular poplar plants removed just 3 percent of the contaminant.

Scientists have recently taken the gene that programs poison in scorpion tails and looked for ways to combine it with cabbage. Why would they want to create venomous cabbage? To limit pesticide use while still preventing caterpillars from damaging cabbage crops. These genetically modified cabbages would produce scorpion poison that kills caterpillars when they bite leaves — but the toxin is modified so it isn’t harmful to humans.

GM Cows

a calf whose milk could be drunk by people suffering from lactose intolerance

a second animal whose milk contains high levels of "healthy" fat found in fish.

2011, China: The scientists have successfully introduced human genes into 300 dairy cows to produce milk with the same properties as human breast milk.  the researchers said they were able to create cows that

produced milk containing a human protein called lysozyme They created cows that produce another protein from human

milk called lactoferrin, which helps to boost the numbers of immune cells in babies. A third human milk protein called alpha-lactalbumin was also produced by the cows.

Synt-ethics

On May 21, 2010, Science reported that the Venter group had successfully synthesized the genome of the bacterium Mycoplasma mycoides from a computer record, and transplanted the synthesized genome into the existing cell of a´Mycoplasma capricolum bacterium that had had its DNA removed. The "synthetic" bacterium was viable, i.e.capable of replicating billions of times.

Artificial life

Mycoplasma mycoides 1,08 Mb

„synthetic cell“ – only its genome is truly synthetic

Synthia

Craig Venter: "the first species.... to have its parents be a computer" James Joyce: "To live to err, to fall, to triumph,

to recreate life out of life"  Robert Oppenheimer: "See things not as they

are, but as they might be".  Richard Feynman: "What I cannot build,

I cannot understand"

Artificial lifecritics

Frankencell!

Artificial lifecritics

the potential benefits of synthetic organisms have been overstated.

By releasing these „synthetic organisms“ into areas of pollution, we may actually releasing a new kind of pollution. We don't know how these organisms will

behave in the environment.

Artificial life

in the near future we may switch from „reading“ the genomes to „writing“ them

the time of „digitizing biology“ is about to come

the software builds its own hardware

Artificial life

may one day metabolize the oil metabolize the carbon dioxide and thus

reducing the greenhouse effect making a new types of fuel farmacology: making a new vaccines etc.

"The Lego-ization of biology"

Discussion

Modifikace stejně děláme...

Biomedical Research

Bioterrorism Bioerrorism

"superweed" etc.

strains of microorganisms to be used in recombinant DNA experiments are genetically crippled to ensure that they cannots survive outside the laboratory.

Biomedical research

Precautionary Principle When in doubt, pause (mostly Europe)

Proactionary Principle When in doubt, go ahead

(Thomas Murray, http://www.youtube.com/watch?v=1y4jt7oDrZI)

Biomedical research

Precautionary Principle When in doubt, pause

(mostly Europe)

Proactionary Principle When in doubt, go

ahead (Thomas Murray, http://www.youtube.com/watch?

v=1y4jt7oDrZI)

The Presidential Comission for the Study of Bioethical Isues: New Directions: The Ethics of Synthetic

Biology and Emerging Technologies (16/12/2010) "prudent vigilance" "the field of synthetic biology does not require

new regulations"

New Directions: The Ethics of Synthetic Biology and Emerging Technologies8 FEB 2012

public beneficence responsible stewardship intellectual freedom democratic deliberation justice and fairness

„Scientists are making strands of DNA that never existed“ Every two parents who conceive a child are

creating „strands of DNA that never existed“ Church, G., Regis, E., (2012) Regenesis. How Sythetic Biology Will Reinvent Nature and Ourselves.

Basic Books. New York. p. 229

H+

Francis Fukuyama: „the first victim of transhumanism might be equality.“ transhumans, with their heightened powers

better helath, better looks, smarter minds, and longer life spans, would claim comparably outsize rights for themselves.

many of the people coming into synthetic biology today are not biologists. • They are computer scientists, electrical engineers,

mathematicians and physicists who have very little experience with microbiological safety.

synthetic organisms might transferr their genes into exiting organisms and altering the balance of the ecosystem. • might also interact with naturally occuring

substances leading to unexpected consequences. Baldwin, G., Bayer, T., et al. (2012) Synthetic Biology. A Primer. Imperial College Press. London.

loc 2564

enhanced virulence lethality antibiotic resistance greater environmental stability inducing changes in behaviour cause chronic illness be targeted to attack certain ethnic

groups Baldwin, G., Bayer, T., et al. (2012) Synthetic Biology. A Primer. Imperial College Press.

London. loc 2571

biology is not yet amenable to amateur scientists constructing an Ebola virus in their garage.

As the knowledge, tools and techniwues for doing synthetic biology proliferate, it will become increasingly easy for less skilled practitioners, hobbyists or do-it-yourself biologists to do biology, tinker with geniomes and, perhaps, make novel living systems.

What of desktop DNA synthesizers are in every home?

Baldwin, G., Bayer, T., et al. (2012) Synthetic Biology. A Primer. Imperial College Press. London. loc 2602

biology if the trend continues, it might be possible for an amateur viologist to construct a gene of known function in his or her home or garage, and to insert it into an all-purpose chassis purchased from a local biotech supplier.

Baldwin, G., Bayer, T., et al. (2012) Synthetic Biology. A Primer. Imperial College Press. London. loc 2602

amateur biologists test their skills and the practical limits of do-it-yourself biology to invent new, high performance, and possibly dangerous, microorganisms, much in the same way as contemporary computer hackers invent open source software, malware, etc.

„biopranking“• the intentional release of genetically modified

bacteria into a neighbour´s pool that, although intended only to turn the water green, could cause irreversible damage to nearby flora and fauna