Tuesday, April 22, 2014

The Famine of Men

What would happen if, all of a sudden, a few men stopped making testosterone? Did a virus cause the syndrome? Would it spread? What would men do? Would the young virologist who found the first answers be overwhelmed?  In this realistic portrayal of scientists under pressure, the story follows a young scientist as she attacks the problem. The noted University of Chicago microbiologist, Professor Howard Shuman, wrote, “There is no reason that such a virus could not appear. I loved this story and the people in it, even the nasty ones, and I didn’t predict the end.”  You don’t have to be a scientist to enjoy this story – it has been read by novelists, a former lieutenant in the NYPD, professional women and men and lots of other people.  

This is the my first novel, and while it touches on many areas of science and sexuality, it is also my homage to all of the PhD students, post-doctoral fellows and faculty members with whom I have worked for forty years. Forty years ago, a young woman scientist like the hero of this novel would have been rare. Now things are better. As this story will show, that is a very good thing. 

The Famine of Men is available in text and ebook form through AuthorHouse and the author’s website. It can also be ordered on Amazon or most other online sites.



Tuesday, April 8, 2014

Genetically Modified Potatoes and The Irish Potato Failure

In 1845 blight attacked the potato crop of Ireland. A million people died of starvation and another million or more with enough money to emigrate left for the United States and other countries. The blight knew no borders and never disappeared. It did not cause the famine – the failure of British authorities to divert other food to feed starving farmers caused it.  As readers of Jonathan Swift’s A Modest Proposal may recall, it was not the first time.  For the effects of biological blight and the bizarre, but enduring belief that feeding the starving ruins their souls, read Colum McCann’s novel TransAtlantic.

It may seem prosaic to turn from the chronicles of great writers to the blight itself but science can prevent such disasters.  The plants are destroyed by Phytophthora infestans, which resembles a fungus in that it grows rapidly and produces spores that blow on the wind and spread the disease, but is slightly different. Certain wild strains of potato that are constantly under attack have evolved resistance, but Phytophthora thrives on commercial potatoes in the wet weather of northern Europe and New England.  Today, potato growers apply chemical inhibitors 15-25 times to their potato crops late in the growing season to save them, depending on how many wet days there have been. This practice is expensive, leaves chemicals on the plants and soil and compacts the ground as the sprayers move though the fields.

Plant geneticists at the John Innes Institute in Norfolk, UK have shown that there is another way to avoid the blight. The non-scientist can understand a lot of their paper. Using their knowledge of the circuitry of plant resistance to pathogens, they have transferred several genes that provide resistance in wild potatoes into potato cells growing in a petri dish – in this case cells of a potato variety called Desiree.  Plants cells are astonishing in that they can be broken loose from their cell walls and then grown in a stew of nutrients where they divide indefinitely. In this state, small numbers of genes can be injected into the cells by bacterium called Agrobacterium that has evolved a syringe that transfers DNA to the plant.  When these clusters of transformed cells are put on a jelly like surface and hormones are added, they convert into small plants that produce leaves, stems, flowers, and become normal plants with a few extra protein molecules added to the many thousands of different proteins in the plant cell. Grow them in the soil and they make potatoes.

What did the geneticists do to these plants? The potato plant has hundreds of genes that provide the information to make chemicals that are noxious to invaders – think of nicotine and tobacco. Plants are hugely resourceful if they can mobilize their defenses. When the wind-borne spores of Phytophthora infestans, land on the leaves, the plant has a way to detect them. Special proteins protrude through the membrane of the living plant cells and are shaped to bind to molecules on the surface of the invader. When that happens, a signal is transferred by a series of steps to the genes of the plant and it goes into a defensive mode.  It may thicken its cell wall, produce anti-invader chemicals or kill the infected cells so that the infection does not spread.

The Phytophthora and the Solanum (potato) have been at this battle for millions of years. It is an endless game of serve and return. Sometimes the plant evolves defenses and sometimes the invader overcomes them.  The blight cells outwit the commercial plant by injecting interfering molecules that short circuit the alarm system of the potato plant. (These defenses may have been bred out in the development of the commercial varieties.) It is the botanical equivalent of cyberwarfare and left unchecked, the blight wins, as it did with such terrible consequences in 1845.

Wild potatoes, of which there are many varieties in Peru alone, resist Phytophthora. Recall that the fungus-like blight transfers proteins into the plant cells that silence their alarm system. The wild potatoes are one up on the blight and produce counter proteins that inactivate the Phytophthora proteins so that the natural alarm system of the potato cell functions again. 
Rpi-vnt1.1-transgenic and non-transgenic Desiree in field trials: The genetically modified plants are on the left, the standard are on the right. Rpi stands for Resistance to Phytophthera infestans. Vnt-1 is the name of the gene that provides the instructions for the protein that soaks up the injected Phyophthera toxin.

Jones J D G et al. Phil. Trans. R. Soc. B 2014;369:20130087. The Philosophical Transactions of the Royal Society is an open access journal and has been since the 17th century. 
The scientists in Norfolk identified the genes that produce the proteins that protect wild potato plants.  They transferred them into the commercial variety Desiree. Perhaps they restored a status quo ante. They planted these genetically modified plants next to unmodified plants and waited though a wet summer.  The modified plants lived and produced potatoes and the unmodified ones died. The GMO potatoes could not be distinguished from disease-free normal potatoes. British and European Community regulations require that the new GMO potatoes be immediately burned, but knowing scientists as I do, I bet they found some and ate them. If I had used wild potato genes to protect the food supply, I surely would have eaten them.

Monday, April 7, 2014

Does Genetically Modified Corn Cause Cancer in Rats?

The last post introduced forms of genetically modified crops – why they were made and some details of just what the genetic modification is. This is a good moment to discuss this subject because part of the conversation has focused on a particular paper entitled: Long Term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize by a laboratory in France. Roundup is an herbicide discussed in a previous post. Opponents of genetically modified crops acclaimed the paper, thinking at last there was definitive proof of the harm caused by modified corn.  Many scientists found the paper inconclusive and were harsh in their criticism of the Journal. In the end, the Editor-in-chief of The Journal of Food and Chemical Toxicology, retracted the paper. He probably never imagined that he would be in the eye of this particular storm. Some people think the retraction reflected skullduggery by agribusiness lobbyists. No matter how it came about, retraction is a big deal in the scientific (or the journalistic) world.

So I downloaded and read the paper. You might say that I am not a plant biologist but the paper had little to do with plants. It had to do with rats that were fed genetically modified maize. You might say that I am a geneticist and prejudiced in favor of constructive use of genetics. Maybe so, but I have no vested interest in this debate. A former researcher in my laboratory is now head of research for a very large GMO seed company, but he is a large-minded guy and would not be angry if  I supported the Caen scientists. I have reviewed many such papers over the years so reading this one was not a problem. The problem is to explain it without putting readers to sleep.

Let’s start with the rats: The group in Caen ordered a large number of Sprague-Dawley rats from a breeder in France. They are an in-bred strain so that all of the rats were almost identical twins, except that half were male and half female. That eliminates variability, which is good. Unfortunately, individuals from this particular inbred line are known to be susceptible to cancer as they age, and the plan was to keep them alive for two years. This is a problem because cancer is a disease of aging in rats as well as humans. If you want to measure the effect of something (GM corn and Roundup in this case) it is better to measure a change from a low background. A small change is more likely to be random.

Let’s look at the data:  A group of 10 rats got non-GMO corn. Three out of ten of eventually died of cancer. Another group got relatively low doses of GMO modified corn diluted in normal corn. Five out of ten of them died. Interesting, you might say. But the next group got twice as much GMO corn and only one of them died. A third group got three times as much GMO corn and only one of them died. This result does not support the thesis that GMO crops cause cancer in rats. Adding Roundup to the drinking water, improved the results slightly, but there was still no convincing dose dependence, which we would expect. From a statistical point of view, ten rats receiving each treatment is too small a number to give definitive results. And the cancers almost all occurred at the end of the rats’ normal lifespan, when cancer usually occurs.

At various points in the experiment, which lasted two years, the researchers took blood samples and put them through a battery of tests much like a person’s blood would receive at a thorough annual physical. Astonishingly, the authors did not measure Roundup concentration. If they are making the case that the GMO crops cause cancer because of the Roundup, would they not want to see if it or the detergent in which it is often dissolved got into their blood?  For that matter, would you not want to know how much is in their feed? If there is none, how could it cause cancer?

The data are presented in a confusing way and then touted as definitive in a video, but they are not definitive. They are not even good experiments, although showing cancer -laden rats in a video scares people to death. Why not show cancer ridden control rats?

The biggest problem is to explain just how a few new proteins that do not look like toxins could cause the proposed effects. The study proved nothing. See their claims in a video.

Did GMO corn cause this rat's tumor? Probably not!
Are there problems with GM crops? Sure there are, but for a dispassionate view, read Nature Magazine’s analysis of a year ago, which assesses the problem of Round-up resistant weeds.