UCSF scientists placed plant proteins in this mouse cell so that it would respond to light by moving and changing shape. The cell expanded to follow the movement of a red light (circle).

While similar work has been performed in yeast and bacteria, this experiment marks the first time that mammal cells have been upgraded in this fashion. I’m impressed by the way that researchers got cells to move like miniature remote control robots, but there are greater implications. By inserting key plant proteins (called phytochromes) into mammal cells, researchers have created a light-based switch that they can insert into many different chemical pathways. The UCSF team focused on the pathways which affect the cytoskeleton, but they could have targeted protein interactions that control how food is processed, or functions that impact cell life span. Imagine using specially tuned light signals to keep some cells (say those with cancer) from processing nutrients, or encourage other cells (say those in an area with nerve damage) to repair and reproduce themselves. With the protein-based light switch, scientists could change a cell’s chemical functions temporarily, and repeat the process as needed later. That’s an amazingly powerful tool.

When manipulating the mouse cells, researchers used combinations of red light and infrared light. These types of light directly affect the plant phytochromes that were inserted into the mammal cells. Basically, one type of light will induce one kind of chemical reaction, while the other light will stop or reverse that reaction. By bathing the mouse cell in IR and providing a single spot of red light, the researchers were able to get the cell to deform and follow the red spot as it moved over time.

While it took many minutes for the cell to move as the researchers desired, the chemical reactions that the light was causing happened much quicker. The UCSF team was able to control the position of these reactions down to the micron level, and with a response time around one second. This precision could have important implications if surgeons one day used this sort of technique to repair damage in the body. It could also facilitate fine control of the functions of the cell if and when researchers try to control chemical pathways unrelated to cell movement.

I’ve always been impressed with how many technological advancements in biology can be traced to a scientist taking the parts of one living thing and sticking them inside of another. Putting plant proteins in mammal (or some day, human) cells gives us the means to interact with those cells via light. But why stop there? We could have skin cells that produce chameleon pigments or blood cells with the antifreeze from Artic bacteria. Most of this research would seem to be leading towards very controlled forms of transhumanism. Humans have always shaped their bodies to match their needs, but with tools like these we may gain access to changes that are both profound and reversible.

[image credit: Wendell Lim et al, Nature]

Scientists have disabled a single gene to mimic the benefits of Caloric Restriction in mice.

We’ve known for a while that severely limiting your dietary intake, while somehow still managing to get all your necessary nutrients, can extend lifespan dramatically. Caloric Restriction (CR) can increase a mouse’s lifespan by about 50%. Of course, no one wants to eat less so scientists have been pursuing other avenues to achieve CR benefits. We’ve told you about one such possible route: the use of resveratrol, which may (or may not) work. A recently published article in Science discusses another. Dominic Withers from the University College of London extended the lifespan of female mice by 20% using a technique to disable one of their genes. Not only did these mice live longer, they showed greatly improved health at middle age. Withers and his associates may have discovered a genetic fountain of youth.

Life extension has a lot of advocates, notably the Methuselah Foundation and Aubrey de Grey whom we discussed earlier. Most would agree that we need two types of approaches to achieving longevity: a technique that could be applied to people who are already old, and a technique that could be applied from birth or earlier. Withers’ genetic manipulation would be one of the latter. With a single genetic tweak, humans conceivably could be modified in vitro to live longer and healthier. Furthermore, that tweak could become germline (that is, passed on to offspring) so that all future generations of humans had the same longevity. Withers’ work could be the start of a new era of humanity.

There are several competing theories of why CR works, but most focus on interactions between key proteins and cell metabolism. One such protein, mTOR (mammalian target of rapamycin) acts to determine levels of nutrients in the body and helps regulate the body’s response. A study published this July in Nature showed that CR benefits could be generated in mice by dosing them with the drug rapamycin (for which mTOR is named). That’s really exciting. Think about it, life extension just by taking a pill. However, rapamycin causes suppression of the immune system in humans – it is used during organ transplants – and would be unsuitable for use in extending your life.

Don’t worry, we’re not done yet. By studying mTOR’s chemical pathways scientists found another protein, S6K1, and its related gene. It was this gene that was targeted in Wither’s research. He and his colleagues ‘knocked out’ the gene from a group of mice. Essentially that gene was disrupted so that it would not be expressed. The knockout mice displayed some amazing health at 600 days (middle age for a mouse). They had stronger bones, better insulin sensitivity, healthier immune cells, and improved coordination in cognitive tests. Essentially, they had the skills of younger mice. Female knockout mice lived 20% longer.

Unfortunately, the male knockout mice did not. While they displayed the same benefits at middle age, the S6K1 disruption did not grant them longevity. The research team doesn’t know why. However, they have identified other genes and proteins that could be explored to see if more CR benefits could be achieved through genetic manipulation. One protein, AMPK, might yield CR results and it already has a prescription drug associated with it: metformin (used to treat type 2 diabetes).

It is unclear if or when we will start genetically manipulating humans in vitro, but with research like this, that day is more certain to come. A single tweak that could extend life by 20% and let middle aged people feel like teenagers? Parents would be clamoring for the treatment. Longevity in general, whether it comes from a pill, a genetic treatment, or an improved lifestyle, is likely to interest humanity more and more as our population continues to age.

Thanks to gene therapy, this monkey can distinguish shades of red and green.

If nature gave you some bum genes, you’ve got a chance of fixing them. Genetic treatments have allowed researchers to cure color blindness in two squirrel monkeys. As published this month in Nature, gene therapy allowed two males to begin producing the L-opsin protein that allowed them to finally see reds and greens. Besides viewing the world in color, what’s the benefit of genetic treatments? Endless supplies of grape juice. Check out the short video below of one of the monkeys getting a reward for identifying red spots during a test.

When any form of blindness has a genetic cause, the promise of restored sight through genetic treatment lingers. We saw the first such case of gene therapy restoring sight when it was used to cure Leber’s congenital amaurosis (LCA) in human children. Those tests were revolutionary, but monkey technicolor vision is remarkable as well. Most scientists believed that adult brains do not have the same rewiring capabilities and plasticity as young brains. Yet the two adult monkeys, Sam and Dalton, started receiving and comprehending new signals once the L-opsin gene was introduced into their retinas.

All male squirrel monkeys are color blind, making them ideal for the test. Furthermore, the mechanism for their color blindness (the lack of L-opsin protein) is similar to many cases of human color blindness. The same method of gene therapy that was used in the LCA tests, was adapted to help monkeys produce opsin. First, scientists knew which gene codes for L-opsin production. A virus was created to carry that gene. The virus was then injected into the monkey’s retina. Like any self-respecting virus, it infected cells and in the process passed on the new gene. These upgraded cells in the retina now had the gene to produce L-opsin and boom…monkeys see in full color.

While the research was only recently published, it took place over several years. After gene therapy, it took five months of rewards-based testing (like that in the video) to discover that the squirrel monkeys could detect shades of red. It is unclear if that time was due to the slow development or adaptation of neural pathways, or the cognitive progression of the monkeys. In fact, the mechanism for how the monkeys’ brains were changed to receive the new input is not well understood at all. The change is likely very stable – the monkeys have retained their new color perception for the more than two years that have passed since testing began.

The fact remains that we are years from seeing color blind gene therapy being offered to humans. It is obviously still in the animal testing phase. The LCA treatment was for safety testing, not efficacy testing, so there are years of study ahead in that field as well. Still, genetic treatments are advancing and could one day be used to cure advanced macular degeneration (AMD), and other common forms of blindness.

And gene therapy isn’t just limited to the eye. Cures for almost any genetic condition could be done in a similar manner to the blindness treatments. In theory, all it takes to fix an illness is finding the responsible gene and replacing it. We could see these treatments rise in availability in the next ten to twenty years.

Gene therapy could also allow us to update our genes so that we could view colors outside our natural range, or develop low-light vision as good as other animals. Enhancements for oxygen absorption could make super athletes out of everyone.  Such possibilities are likely decades away, but they’re not out of the question.