Old age in good health

A few, thankfully few, children have a genetic disease called progeria. These children age very rapidly and look in their 90s as young children. A couple that are doctors had such a child and formed the Progeria Research Foundation http://www.progeriaresearch.org/index.shtml .

This group interested Francis Collins of the National Human Genome Research Institute (NHGRI) in Bethesda, Maryland who was one of the key players in deciphering the human genome into looking for the gene that causes this disorder. He and his group found it in one year. Now there is a new development, a drug that may reduce the effects of this genetic mutation.

The mutations that cause this disease affect the protein lamin A which appears to be a structural protein in the cell nucleus. The mutant protein causes the cell nuclei of HGPS patients bulge in odd ways, apparently because the abnormal lamin A generated by the mutation accumulates near the nuclear membrane and distorts it. Enzymes called farnesyltransferases help lamin A get to the nuclear membrane by attaching the lipid farnesyl to the protein at a specific place. This makes the protein more hydrophobic and able to attach to the lipid membrane of the cell nucleus. Chemicals that inhibit farnesyltransferases are being studied to keep farnesyltransferases from activating cancer promoting proteins. It turns out in two new studies that these cancer fighting chemicals keep mutant lamin A from distorting cell nuclei. There is hope that such drugs might cure or reduce the severity of progeria.

But, if similar things happen as we all age then could these drugs make aging less painful?

Underwater maintenance

Today was a real strain. I worked on my sailboat and then took it out for a spin. About two miles from port white smoke started to billow out from the stern. I shut off the motor and dropped the hook. A brief examination of the cooling water system showed that there was a blockage at the through hull inlet. Was I going to call the marina or go after it myself? To avoid the embarrassment and cost I decided to don my wet suit and go over the side. After a safety rope was secured to the bow and a bumper placed on the side to indicate the position of the inlet, I hopped over the side hoping that there were no white sharks in the area as I looked rather like a tasty seal. As the inlet is several feet down and I didn’t have a weight belt, it was a struggle to kick my way low enough to pull the seaweed from the inlet. There was a good gob of it. I also had a screwdriver to clean the muscles that had grown in the inlet partially blocking it. The come in as larva and get through the screen but then grow too big to get out. Fortunately there was a hole in the screen that allowed me to get at them. I should have removed the entire screen this Spring as it would have made cleaning the inlet much easier. There is a filter in the boat to keep anything from getting to the motor. The seaweed finished the job of blocking the port. After reassembling the tubing I cranked the motor and water came out the exhaust with no white smoke! As the current was strong retrieving the anchor was a strain. My calves were very sore from kicking with my fins and my back sore from pulling up the anchor. O, the life of a sailor.

stock car racing

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recently had the opportunity to attend stock car races at the Bristol Motor Speedway in Bristol TN. We were in a sky box that was air conditioned with glass windows to reduce the noise. As with any sport it is more interesting when an enthusiast explains what is going on. There were a few crashes with no injuries but most of the delay’s were do parts falling off cars. The raceway holds 200,000 fans! This is a big event in the area. Why? Other than the crashes not much happens but it is a good reason for an outing with lots of eating, drinking and hot sweaty people.

Return from pacemaker implant - What the bleep do we know

Hi Steve, Today I returned from Ohio and Mom's pacemaker insertion. It seemed as if the device was greatly needed and that she may have fainted with hurtful consequences if the operation had not been done. The procedure took about an hour and a half a on Friday with recuperation in the ICU until Saturday afternoon with transfer to a room on the same floor. She had a monitor for the full say which ended today in the late morning. Gary and I took her home followed by a nice brunch at the Catawba Island Club enjoyed by all. I also talked to a couple of boat owners at the docks. Mom seemed to do well through the ordeal and hopefully we will have avoided a major problem though at this age one can't tell. After visiting hours on Saturday I met Gary, Gary D. and his wife Sue a rock band concert at the Mon Ami restaurant on Catawba Island. It was loud and we soon went home for beer and pizza with some cheese and wurst. It was fun talking about old times. On Sunday after brunch I took off for the airport and my flight home through Baltimore. During the flight I finished the book "Beyond the Bleep" by Alexandra Bruce which was a commentary on the film "What the Bleep do we Know?" This book brought out the association with many of the principals in some new age groups and especially one that makes a lot of money called Ramtha that is based on some women channeling a spirit that is around 25,000 years old. This makes the film more questionable although some well credentialed scientists participated in the film.

pacemaker

My mother at 85 has just had a pacemaker implanted. She seems to be doing well and the device is pacing quite often suggesting that she really needed one. It is interesting to watch the trace of the electrocardiogram in real time and see how often the pacemaker switches in to help things out. She was at the dentist and for some reason then did a blood pressure and found it off the chart. A quick drive to the hospital and an overnight ECG resulted in a pacemaker the next day. Hopefully this will give her many more years. She golfs three times a week wining tournaments in her age class. She may do even better now.

Another blog - Genetic Chaos

This is an interesting site for the study of human migrations including those of the Finns and Lithuanians. The study of "race" is not always PC and I don't know if there are any undertones here but the science sound good.

Are we part Neanderthal?

I was just watching a PBS program on human evolution. The show was well done. It ended with DNA and Neanderthals. The results seemed to show that we are not closely related to Neanderthals although we must have come from some common ancestor. I believe that this work was with mitochondrial DNA as it is the most prevalent form of DNA with hundreds to thousands of copies per cell. Most genes are of course only present in two copies per cell. It may be that looking at nuclear genes would show a closer relationship with some interbreeding in Europe. Mitochondrial genes can be lost as they are only inherited maternally and if a women doesn’t produce a daughter her line will become extinct. In fact, considering how the Neanderthal looked it may be that any interbreeding came by a male Neanderthal mating with a human female. I assume that do to her strength, a Neanderthal female would not be susceptible to rape. The other way around sounds more reasonable.

The advantage to mitochondrial DNA is it’s many copies per cell compared to the two copies of nuclear DNA per cell. There is another form of nucleic acid that is also present in many copies per cell and it includes nuclear genes. It is RNA. It can be present as messenger or ribosomal RNA as well as other forms. I believe that it is less stable than DNA and more prone to degradation with age. However, there is a lot more of it and would show genes inherited from either parent. One would use reverse transcriptase to convert the RNA to DNA for sequencing. Looking at nuclear nucleic acids may yet show a closer relationship between Homo sapiens and Neanderthal.

Also, in the documentaries the Neanderthal are shown with dark hair and brown eyes. As they spent over 200,000 years up North I would assume that they would have a greater tendency to be blue eyed blonds than humans. Perhaps blond hair, blue eyes and light skin are Neanderthal traits.

Jeeps can be expensive

My jeep has over 250,000 miles and is costing me a lot. Perhaps it is time for a change. Earlier this summer they put in a new condenser for the air conditioning for a cheap $800. Today I took it in for the yearly inspection. The emergency brake was weak and hopefully just needs an adjustment. However, two tires were bad, one on the front and the other on the back. It seems that Jeep at the time had different tires on the front and the back that could not be interchanged. So I just get one of each, right? No. Goodyear no longer makes the tires so they tried to sell me four new tires even though two were in good shape but neither could be put with the other. I suggested that they use my spare and buy one tire that is close to what is required. Hopefully that is what they will do. Perhaps this $30 inspection will cost me less than several hundred dollars but I am not holding my breath.

drug discovery

This week Boston's hosts a meeting on drug discovery at the new convention center. New drugs are still the results of endless and sometimes mindless testing of candidate chemicals on biological systems. There is a major attempt to make the discovery process more rational using the human genome sequence information and a better understanding of drug targets such as protein receptors. There is a long way to go. The exhibits show an almost endless array of robotic chemical processing systems to speed up the process. Also, now we have RNA chips that can look at the activity of 30,000 genes in a single experiment. This is done to see which active genes are affected by a specific chemical. Such “gene” chips should also be useful at identifying potential side effects before clinical trials. If the product of a critical gene is depressed then there is a good chance that one will see bad things happen in the clinical trials. A current problem is that while we can see which genes are active many of them have no known function. As time goes on most we will learn the function of most of the genes and the techniques will become more useful. It can only get better.

End of reunion

My wife's twin brothers and families have all gone home. It was a great time from Old Ironsides to the Freedom Trail to sailing in Maine to many great meals and conversation. Everything worked and no one got hurt.

We want cures. NIH should focus on cures not therapies

I have been thinking about NIH, Government grants and Drug companies. The money is in therapy not cures. A drug company prefers a therapy because the poor patient never gets cured and has to continue sometimes forever taking the stuff. Cures are much better for the patient but it is difficult to pay fairly for them. Antibiotics are a good example. They can cure you. If you have a microbial infection that would kill or severely debilitate you an antibiotic can cure you of this disease. You take the drug for a while and then stop taking it after you are cured. Being cured is worth a lot of money but we don’t pay for it. Antibiotics became cheap do to market pressures and there was little money in their production and sale. Therefore the pharmaceutical industry has little interest and the development of new antibiotics almost stopped. Then came organisms resistant to the antibiotic and it no longer worked. However, there were few in the pipeline so that the number of effective antibiotics available went down. If we had just paid proportionally to the value received then the pipeline would have been full and we could have more effectively addressed the resistance problem. It is easy to develop resistant organisms. In microbiology labs we did it all the time by growing billions of bacterial in the presence of the antibiotic and selecting the colonies that grew. They were composed of bacteria that were resistant to the antibiotic. Fortunately, such resistant bacteria usually give up something to become resistant and do not do as well competing with other bugs when the antibiotic is absent. This is why we don’t want to over use antibiotics. If we keep the antibiotic there then we will continually favor the resistant bugs.

NIH and other government agencies in the healthcare area should focus their research on cures. The drug companies don’t like cures but will readily develop therapies because that is where the money is. The drug companies will take care of the therapies but without NIH there will be little focus on cures.

Dogs and cultural development

Well it has gone to the dogs, at least in Korea. A group in Korea has created the first cloned dog and won a race with a well financed American firm. The development of Korean science has been impressive and this is just another example. One wonders what it is tha allows them to advance while similar nations with even more resources can’t seem to get it together. The have been oppressed by the Chinese and Japanese for centuries. Other nations with less to show for their efforts complain about a colonial past but if such passed oppression is the excuse then why have Korea, Taiwan, Singapore and others such as the U.S. done so well. I was in Korea a number of years ago and was impressed by their work ethic and their respect for technology. I believe that the major factor is attitude and a willingness to work hard. The only other explanation is that they are genetically superior which I don’t believe. We are all very similar genetically having evolved from a small group of individuals that existed on the brink of extinction about 150,000 years ago.

Back to the farm

Today was Rotary with the largest attendance we have had in many weeks. Our new leader Hum is doing a great job. Afterwards I helped put 150 bales of hay in the barn. I grew up on a farm and went to school forever so that I wouldn’t have to toss hay and muck stalls. So much for a life plan. My wife’s brothers and families should start arriving today. We will have a full house but it should be fun. Yesterday I went to work on the boat and found a loose wire on the ignition switch that had been causing the intermittent problems. Hopefully this is the last problem for a while.