Posts Tagged ‘genetics’

The 1918 flu pandemic

Wednesday, December 31st, 2008

Genetic engineering may have explained the mortality of the 1918 flu. Apparently, three genes are responsible for the viruses ability to infection lung and not just bronchus.

“We wanted to know why the 1918 flu caused severe pneumonia,” Kawaoka said in a statement.
They painstakingly substituted single genes from the 1918 virus into modern flu viruses and, one after another, they acted like garden-variety flu, infecting only the upper respiratory tract.
But a complex of three genes helped to make the virus live and reproduce deep in the lungs.
The three genes — called PA, PB1, and PB2 — along with a 1918 version of the nucleoprotein or NP gene, made modern seasonal flu kill ferrets in much the same way as the original 1918 flu, Kawaoka’s team found.

There was a second reason for the high mortality in 1918-1920. The principles of thoracic surgery, including the physiology of respiration were not understood at the time. Thousands of flu cases, those with pneumonia, developed a secondary bacterial pneumonia and then developed empyema. Empyema is a collection of infected fluid in the space between the lung and the chest wall. We now know how to treat this condition. The principles of treatment are here. Note the observation that Hippocrates understood the principle of empyema; namely that thin fluid in the collection could be drained by an opening in the chest wall but the patient would die. Hippocrates didn’t understand why. The knowledge of lung physiology would not come until the 19th century. However, Hippocrates did observe that draining thick pus through an opening in the chest did not result in the death of the patient in all cases, as it did in those where the fluid was thin and watery. What was the reason ?

We now know that a relative vacuum exists between chest wall and lung. The chest wall is rigid and, during respiration, it changes its volume by using the “bucket handle effect” of the ribs.

The space between lungs and chest wall is shown along with the general anatomy. That space is what fills with fluid in cases of pneumonia that develop empyema.

The ribs are curved and, when the muscles of the chest wall pull up on them, as shown by the arrows, the cross section of the chest cavity increases because of the “bucket handle” effect. With expiration, the ribs move back down and the volume of the chest cavity decreases. This volume shift, aided by the piston effect of the diaphragm, moves air in and out of the chest. The lungs are not attached to the chest wall, allowing them to slide up and down and accommodate their shape to the shape of the chest wall. If there is a hole in the chest wall, the air can move into the space between the lung and chest wall, collapsing the lung. This is called a “sucking chest wound” in trauma care. If the hole in the chest wall is larger than the trachea, air will move more easily in and out of the chest and respiration through the trachea will stop. This was the great barrier to chest surgery that was not overcome until the 1920s. The flu epidemic, and the research into the cause of death in so many cases, led to the understanding of how the chest works.

I recently reviewed a book about the history of the 1918 flu epidemic and, because it ignored the issue of empyema, I could not finish it. They had only half the story. The story of empyema, and the cause and cure, resulted from work of the Empyema Commission, chaired by Evarts Graham, professor of surgery at Washington University of St Louis medical school. Here is one of many scholarly works describing his great accomplishment. Unfortunately, little of this has penetrated the general history of the epidemic in spite of 90 years. In a recent article about the military cases during the First World War, it states: During World War I, the overall empyema mortality rate among US military forces was 61%. The same, or greater, mortality was seen in the flu cases that occurred in the same period. Untreated empyema was virtually 100% fatal.

During World War I, empyema treated by thoracotomy was associated with a mortality of > 30%. This prompted the establishment of the Empyema Commission, which recommended chest tube drainage for treatment.

The surgeons who were treating the flu cases, just as those treating empyema due to war wounds, used the old Hippocratic treatment of draining the pus from the empyema. Note that in the war wound cases, 70% of these patients survived. The flu cases were different and almost all died in a few hours after the fluid was drained. The difference was that the empyema in flu cases was due to streptococcus infection, which produces a thin fluid and does not cause the lung to stick to the chest wall. When the chest was opened, the lung collapsed and these already sick patients succumbed. Hippocrates had predicted this. The war wound cases did better because the staph infections of the pre-antibiotic days (“Laudable pus”) caused the lung to stick to the chest wall and it would not collapse.

Eventually, Graham learned that using a tube instead of an open hole to drain the pus, and placing the chest tube under water at its lower end, would seal the air leak but allow drainage of the pus. His work opened the door to thoracic surgery and, today, would save most of the cases in a new flu epidemic. Graham was also the first to warn of the association between smoking and lung cancer, a disease he was to die of 1957. He performed the first successful removal of a lung for cancer and his patient attended his funeral 24 years later.

Genetics is a powerful tool in the treatment of disease but physiology is still as important. Scientists understand the first but may not be aware of the other factors. There is no substitute for the experience of treating patients.

Science ignorance and the press

Tuesday, July 15th, 2008

John Derbyshire today has yet another example of people writing about science who don’t understand it, even a little bit. I have a lovely daughter who has an honors degree in Anthropology. Unfortunately, she got indoctrinated in the “Blank Slate” theory of child psychology, as promoted by “Mismeasure of Man” author, Stephen Jay Gould. The blank slate advocates are enthused about molding children’s minds and include behavioral psychologists as well some rather scary characters from Stalin’s USSR who were going to invent a “New Soviet Man.” This is all about politics, you see.

Steven Pinker actually wrote a book called “ The Blank Slate, which should have debunked much of the behavioral nonsense. I tried to get my daughter to read it when we were on a trip together but she refused. Pinker shows from identical twin studies that much behavior is inherited. We can argue about nature vs nurture all day but to assume that behavior is all one or the other is to risk being shown a fool. Unfortunately, the nurture assumption has gotten involved in politics and that skews the debate.

Then along came The Bell Curve, which makes one point that low IQ people seem to be having more children than high IQ people and scared everybody into thinking it was racist. In fact, it was nothing of the sort but facts are less important than rumors in some political circles. I was at Dartmouth when it came out and it was hilarious to see people, who would not be seen buying the book in the Dartmouth Bookstore, quietly asked me to borrow it when I finished.

David Brooks seems to be in that category as Derbyshire quotes him:

Prof. Eric Turkheimer of the University of Virginia, conducted research showing that growing up in an impoverished environment harms I.Q.

Lysenko would be proud of Brooks for that howler. Turkheimer actually didn’t say that but Brooks confuses low income and intelligence of parents who have low income and intelligence children with environmental influence.

Children reared in low-SES (socio-economic status) households, therefore,
may differ from more affluent children both environmentally and genetically
(Gottesman, 1968), and the models we employed in this
study do not allow us to determine which aspect of SES is responsible
for the interactions we observed.

It’s only a step from that to say that environmental influences will affect inherited characteristics like IQ. That is at the root of Gould’s theory of the Blank Slate. The child is like every other child, capable of responding to environment or parental influence to become more intelligent or more aggressive or passive. It’s only a step to the New Soviet Man.

Central to Lysenko’s tenets was the concept of the inheritability of acquired characteristics.

There seems to be a general feeling, as a Hastings Center working group put it, that “behavioral genetics will never explain as much of human behavior as was once promised.”

No. Feeling it may be but it is not true. Do some reading.

How about an IQ test for reporters and columnists ?

Craig Venter

Thursday, March 20th, 2008

Bradley Fikes and I spent the afternoon at UCSD to hear Craig Venter speak. I was not disappointed. I wrote the first review on Amazon of his autobiography and he knew this today, commenting that it was the most credited as “helpful.” His accomplishments go well beyond medicine although that seems to be the part that fascinates reporters.

He discussed the sequencing of the genome but the most important part is the environmental potential of his work. For example, the methanobacteria are now properly known as Methanococci as they are now known to be a member of Archaea, a new kingdom of life. If you really want to know about Archaea,
this is the source
, although a PDF version can be downloaded and printed. These organisms can exist at the extremes of nature, such as steam vents on the ocean floor.

Some of them are capable of regenerating oil or natural gas from CO2. Some can metabolize coal in underground deposits and release methane gas. Some can metabolize sulfuric acid and release metallic sulfur and water. Some bacteria can generate nanowires and potentially function as a battery with electricity generation from animal waste.

Some of them will take up uranium and some may even be able to metabolize radioactive elements. Some may function as a bacterial fuel cell. Some of these fuel cells involve bacteria with nanowires. These systems are getting close to practical use.

The great advantage of all of these systems is that energy inputs are far less than the inorganic equivalent, such as burning or conversion to ethanol of plant substrate. The bacterial systems can convert the substrate directly to methane or a higher carbon molecule by enzyme action that takes place at ambient temperature.

Methane has one carbon. Ethane has two and octane, the ideal form of gasoline, has eight. These systems may be the way to refine tar sands or high sulfur crude oil that is not yet economical to use as fuel. Some of them will make fuel from waste. Some may even reduce nuclear waste to safe deposits that do not require isolation.

Right now, Venter is working on ways to analyze the genome of organisms with exotic properties and transfer the gene to more common or faster growing organisms. His company is called Synthetic Genomics. and is in southern California. He has other companies in the east but this application is more important, I think, than the medical applications right now. He calls it “digitizing life” and says that creating a synthetic chromosome is not difficult. The problem is “rebooting it.” He is about to announce an artificial bacterium and I thought the announcement might come today. It will be soon.

We’ll see what the next steps are.

More on synthetic biology

Monday, December 17th, 2007

UPDATE:  Bradley Fikes has been bugging me to add a correction to this post. His argument, which I acknowledge without really buying it, is that the discovery of DNA Polymerase by Kornberg in 1958, qualfies as “created DNA in a test tube.” His work received a Nobel Prize but I’m not sure it merits this statement: “It has been 50 years since scientists first created DNA in a test tube, stitching ordinary chemical ingredients together to make life’s most extraordinary molecule. ” He discovered the mechanism for DNA synthesis and was able to produce nucleotide chains. Anyway, maybe Badley has a point.

The Washington Post today  has a piece on synthetic DNA that is interesting although it contains a few errors. The first is that scientists did not “create DNA” 50 years ago. Watson and Crick, with a lot of help from others, some of whom they neglected to credit, discovered that DNA is the genetic code. In 1983, Kerry Mullis discovered the polymerase chain reaction, which will make thousands of copies of a small fragment of DNA. This allows the use of DNA in forensic science, as in the “Innocence Project” which uses DNA found at a crime scene to be magnified to measurable amounts for analysis. It still isn’t “creating DNA”, it is merely copying it.

Aside from that quibble, and there are probably a few other errors I don’t recognize, the potential for this technology is enormous. I have previously posted on this topic but it is interesting to see it in the main stream media, errors and all.