Sunday, November 23, 2008

Book Review: What is Life?

Anyone who has taken introductory biology is familiar with the stories of Mendel, the discovery of DNA, and Charles Darwin's adventures with evolution and natural selection. What most of these people probably do not realize is why this material is relevant in the modern age of molecular biology.

Ed Regis's book What is Life? Investigating the Nature of Life in the Age of Synthetic Biology takes the reader on the journey from the 1943, and the publication of Erin Schrodinger's What is Life? to the labs of modern day biochemists, cell biologists, and geneticists, who are beginning to unravel some of the fundamental questions about life. The book explores how we, as scientists, have reached the ability to develop life in the lab. This is often called synthetic biology, and it is frequently thought of as being the stuff of science fiction. Several of my blogs have covered topics relating to synthetic life (for example, see Synthetic Life Makes Synthetic Proteins), most because this is going to be a hot topic for society in the next few years. For as Ed Regis points out in his book, the work is already underway, and scientists are getting closer to unlocking some of the secrets of what it means to be "alive".

For those students who are burdened with a heavy reading load, or those non-students with hectic lives, this book is a mere 171 pages in length. Better yet, it is written in a non-technical style that brings to life many of the historical people in the study of the life sciences. It is an easy read, and anyone who has an interest in understanding science should check out this book.

Tuesday, November 18, 2008

The Death of Junk DNA and Birth of the Junkome

Not so long ago, geneticists considered the vast stretches of non-coding regions in DNA to be “junk,” nothing more than the remnants of our evolutionary history. If it wasn’t a traditional gene, and didn’t produce a protein, it wasn’t of interest to most scientists. Luckily, not everyone considered these regions of DNA to be junk. Some considered the junk DNA to be the dark matter of the genome. They believed that it must have some function, but no one had yet determined exactly what that function was.

One of these individuals is Dr Craig Pikaard at Washington University- St Louis. His research group has discovered another use of junk DNA – it acts as a component of the cellular immune system by enhancing the ability of the cell to combat infection by viruses and transposons (also known as “jumping genes”). In a recent manuscript published in the journal Cell (vol 135 #4) Pikaard and associates demonstrate that in Arabidopsis , the fruit fly of plant genetics, the RNA polymerases within the cell use these non-coding regions of DNA to silence viruses and transposons. RNA polymerases are normally active in the process of transcription – the first stage of gene expression. Pikaard’s work suggests that these regions of “junk” DNA may be important in the generation of small interfering RNAs, so siRNAs. siRNAs are known to be involved in the silencing of genes by interfering with the transcription process. The medical community is very interested in the use of siRNAs in the prevention and treatment of diseases. Pikaard’s discovery in Arabidopsis should pave the way for additional studies in animals.

It seems that the time has come to let the term “junk DNA” fade into obscurity. In its place lets use the term “junkome” – those regions of DNA that we have no idea what they do, but agree that they must do something. After all, assuming something does not have a function because we do not understand what it does is not a lesson that we should be teaching young scientists.

WUSTL news release

Wednesday, November 12, 2008

Dr Google

Is there anything that Google can't do?

An article in the NY Times ("Google Uses Searches to Track Flu's Spread") by Miguel Helft reports that Google may be able to detect outbreaks of influenza up to two weeks earlier than the Centers for Disease Control (CDC). According to Google, people who have the symptoms of the flu search for terms such as muscle aches and flu on the search engine, and data-mining of these searches can help pinpoint outbreaks in advance.

There are several alarming items that can be derived from this report.

  • Google is faster at reporting medical events, epecially outbreaks, than the CDC. Maybe we should not be suprised by this since the CDC is a government agency, but one has to wonder what is in this for Google. After all, Google is a for-profit (and big profits!) business, and we may want to be careful about turning over reporting to a private company.
  • People search the internet before seeing their doctors. We all knew that this was the case, and we have all done it. Who wants to sit in a doctor's office for 3-4 hours when they are sick? But this also means that people are using Google as their primary first source of medical information. Anyone who lives on the web knows the amount of garbage that exists in cyberspace.
There is also some good news from this study.

  • We all know that the government is not known for its ability to respond rapidly. The use of the studies by both Google and Yahoo! may help develop a more rapid response plan. Maybe we don't need it for influenza, but other outbreaks, such as SARS and Avian flu, may require a faster response time than the CDC can currently supply.
What would be interesting is if Google informed the medical community on where these people were going to get their information on the web. Is it a reliable source, such as WebMD, or is it Bob's Influenza Shop? Maybe then the medical community can start to use the web effectively to deliver useful information to the public.

Sunday, November 9, 2008

The Return of the Sloth?

Around 10,000 years ago, in the region of the United States now known as the Appalachians, lived one of the most impressive mammals ever to inhabit North American. With a height of over 8 feet, and weighing up to 800 pounds, the giant ground sloth ( Megalonyx jeffersonii to scientists) was a formidable sight. However, the ground sloth, like most large land mammals in North America, went extinct. Why is still a mystery to scientists - some believe that it may have been the result of a change in climate, others suggest that it may have been from predation by humans.

Such is the case for many species, and it is the basis of Darwinian natural selection. Those species that have the genetic variation to adapt to a changing environment do, and those that do not go extinct. Unfortunately, humans have been changing the environment a little faster than most species would like. Many ecologists and biodiversity experts believe that we are experiencing a mass extinction event unlike any in the past 65 million years. And, until recently, we had few choices to prevent the extinction of a species - we could either put it in a zoo, or try to conserve its natural habitat. While both have had some success, most of the news from the conservation front is not good.

Some have asked whether it may be possible to clone extinct animals using the DNA from frozen tissues. Until recently, the majority of attempts to do this have failed - mostly because the DNA was damaged by the process of freezing. DNA is a durable, but also delicate, molecule. Its structure protects it for long periods of time, but even slight damage to its information-containing bases can be troublesome. That may have changed with a discovery by Teruhiko Wakayama, a Japanese developmental biologist. Wakayama has found a way to use frozen DNA in a cloning process. His process appears to reduce the influence of damaged DNA, allowing previosuly unsuitable tissues to be used in the cloning process. Once a cell line is cloned, it could be used to revive an extinct species.

For the ground sloth, passenger pigeon, and the dodo bird, this may be the resurrection that the species needed. Not only could we finally right a terrible wrong in our human history, we may be able to prevent (or at least postpone) the extinction of some species that are currently struggling for survival. Of course, no one is actually (yet) suggesting that we can bring back a giant sloth, but if we can perfect the process, then someday hikers along the Appalachian Trail may have more to deal with than just brown bears.

Additional References:

Wakayama's 2008 paper in PNAS

Monday, October 27, 2008

The Battle Against Viruses Heats Up

Viruses are nasty opponents, as anyone who has followed the battles against influenza, SARs and HIV/AIDS can attest. They are diverse and in many cases evolve at rates that confound efforts to contain them. Anyone who has gotten a flu shot, and then came down with the flu a few months later because the “strain” of virus that the vaccine was not the same as the “strain” that they were infected with, knows just how fast viruses can evolve. In many cases, medical professional never really know which virus has caused the symptoms in their patients, and this complicates treatment and often leads to the misuse of antibiotics, which, of course, are never effective against viruses.

At the ScienceWriters 2008 New Horizons in Science meeting at Stanford University (sponsored by CASW) this week, Dr. Joseph DeRisi of UCSF presented an interesting talk on his research to develop a new form of “chip” as a diagnostic tool for identifying the viral contributions to diseases. Gene chips are often used by molecular biologists to determine the relationship between a gene and an observed condition. Dr DeRisi's work takes this approach one step further.

What is interesting here is Dr. DeRisi’s application of evolutionary genomics to his work. Like microbiologists, virologists recognize that they have only identified a small fraction of the diversity of viruses that are out there in the natural world. Despite advances in sequencing technology, the ability to sequence every virus in a given environment, such as a fecal or nasal sample, is still not cost effective. However, what Dr DeRisi has done is to develop a “viral chip” that contains not the entire sequences of every virus, but rather the sequences of key genes that are evolutionarily important to certain families of viruses. When one of these viral chips is exposed to a sample, a computer program determines the level of similarity between the DNA (or RNA) in a virus and the sequence on the chip. For previously unknown viruses, this can allow a quick classification of the virus to a certain group, and has been proven to be very successful by Dr. DeRisi’s team in diagnosing diseases for which no known cause could be determined by diagnostic tools.

Furthermore, Dr DeRisi has proposed making these chips available at cost to the medical community through a non-profit organization. The availability of a new technology at an inexpensive cost would represent an important new development in the war against viruses, and would rapidly generate an increase in data for public health officials.

Additional Links

DeRisi Lab at UCSF

Saturday, October 25, 2008

Fruit Flies Enter the Political Battle

The political fray has entered into the world of genetics, and as usual, our politicians have no real idea what they are talking about. In an October 24th speech about children with special needs, Sarah Palin, the Republican nominee for Vice-President, made the following statement about funding for IDEA, or the Individuals with Disabilities Education Act.

“This is a matter of how we prioritize the money that we spend. We've got a three trillion dollar budget, and Congress spends some 18 billion dollars a year on earmarks for political pet projects. That's more than the shortfall to fully fund the IDEA. And where does a lot of that earmark money end up? It goes to projects having little or nothing to do with the public good -- things like fruit fly research in Paris, France, or a public policy center named for the guy who got the earmark. In our administration, we're going to reform and refocus. We're going to get our federal priorities straight, and fulfill our country's commitment to give every child opportunity and hope in life” (Oct 24, 2008 speech)

There is no doubt that more money needs to be spent on research and education of people with disabilities. However, the assumption here is that fruit fly research is a waste of time and money. Nothing could be further from the truth. The simple fact that we have an understanding of genetics can be traced back to Thomas Hunt Morgan and the first use of fruit flies.Since then, four Nobel Prizes, including one to Thomas Hunt Morgan (1933), have gone to "fruit-fly" researchers. Obviously the scientific community values the contributions of the fruit fly to the study of genetics.

The fruit fly Drosophila melanogaster has around 19,000 genes. In humans, if a disease is linked to a specific gene, there is around a 70% chance that a similar gene exists in Drosophila. Drosophila is a model organism for the study of many human-releated diseases, including behavior, aging disorders, Parkinson's, and Alzheimers

Research into Drosophila genomics paved the way for the Human Genome Project. In other words, research using fruit flies, and other model organisms such as the mouse, nematode (C. elegans), and weed (Arabidopsis thaliana) are critical towards our understanding of the molecular world of inheritance and disease.

Time to get some Straight Talk. We owe thanks to geneticists who use this model organism, not ridicule.

Additional links:

A Brief History of Drosophila’s Contributions to Genome Research

A Systematic Analysis of Human Disease-Associated Gene Sequences In Drosophila melanogaster

Homophila: human disease gene cognates in Drosophila

Thursday, October 9, 2008

2008 Nobel Prize in Chemistry

The Nobel Prize in Chemistry has been announced, and this year, three scientists received the Nobel Prize for their work on green fluorescent protein (GFP).The three were Martin Chalfie (Columbia University), Roger Y. Tsien (UC - San Diego) and Osamu Shimomura (Marine Biological Laboratory, Woods Hole, MA). Anyone who has watched the Discovery Channel has seen the images of jellyfish glowing in the depths of the ocean. These scientists not only isolated the fluorescent protein from the jellyfish Aequorea victoria, but found a way to link it to an antibody to identify other proteins in a cell. When the cell is exposed to a certain wavelength of light, the tagged protein fluoresces, showing the location of the tagged protein.

Aequorea victoria

An image of a GFP labeled cell from the website of
Dr. Robert S. McNeil at the Baylor College of Medicine

As an interesting coincidence, I had the opportunity yesterday to attend a seminar at Appalachian State University given by Dr. John Henson of Dickinson College, PA. His area of expertise is cell biology, and specifically the structure and function of the cytoskeleton in sea urchin cells. What made his work truly impressive were the images. The detail and resolution that the GFP provided in the images was astounding. I can't imagine Dr Henson being able to present his findings without the use of GFP. I am sure that researchers and educators around the world would agree that Nobel Prize in chemistry was justly awarded.

Additional Links:

New Scientist's slideshow of how GFP has been used in research.

Announcement from the Nobel Foundation.

Tuesday, October 7, 2008

Good News, and Old News, about HIV

There were several important announcements in the HIV/AIDS battle this week. First was the awarding of the Nobel Prize in physiology or medicine to two French virologists,Françoise Barré-Sinoussi and Luc Montagnier, for discovering that the HIV virus causes AIDS. The side story here is the controversy that the American scientist Robert Gallo is credited by some as being the "first" to discover the virus. "First" is very important to scientists, therefore, there have been some pretty heated exchanges between Montagnier and Gallo in the past. If you are interested in some good drama, there are some decent books out there on the subject, including opposing views written by both Gallo and Montagnier.

The Nobel committee has attempted to end the dispute by announcing that Montagnier was the discoverer, a fact that is widely accepted by the scientific community, but given that there is no love lost between the Americans and the French, it is doubtful that this will die down soon.

The second announcement was that the HIV virus is probably much older than we originally thought. A discovery at the University of Arizona by Dr. Michael Worobey backs the date that the virus jumped from chimps to humans sometime around 1900 - at least 30 years earlier than originally thought.

This should not be treated as some sort of background story. In fact, it is probably the most important, and under-reported, story of the week. If you take a look at the map from the CDC below, you can see that the AIDS pandemic is showing no signs of abating.

By understanding when the virus actually made the jump from chimps to humans, we can get a better grasp on its rate of evolution. One of the biggest obstacles to the development of effective HIV vaccines has been the rapid mutation rate of the virus. As a virus mutates, it evolves, or changes, its associated proteins. Vaccines frequently target the unique proteins on the surface of a virus. Without an understanding of how this virus is continuing to evolve, the development of a vaccine could actually create more harm than good, since vaccinated people may feel that they are "safe" and can return to unsafe sexual practices and other risky behaviors. Worobey's work should provide some important insight into how HIV evolves. We should be seeing some interesting developments in the near future stemming from this discovery.

Saturday, September 27, 2008

The Question of Fragile X

Geneticists really need to work on naming their genes. Drosophila geneticists are the worst - we give genes names such as Grunge, grim reaper, and swiss cheese (see a great link here), but sometimes the human geneticists can slip as well. One example - the fragile X syndrome. The name fragile X suggests that this version of the X chromosome is like a Ming vase...delicate and susceptible to fragmenting. But in reality, it causes a much worse condition.

What happens in fragile X is that there has been a duplication in a portion of the DNA on the X chromosome. Duplications happen all of the time, but unfortunately, this one happens to occur within the coding region for a gene. This gene is FMR-1, and it appears to be a very important gene for humans. FMR-1's gene product, the fragile X mental retardation protein (FMRP)is responsible for development of the neurons - the cells that conduct billions of electronic messages in our bodies, and brains, per second. In the mutated form of FMRP, there has been a repeat in one of the instructions, commonly called a codon. The repeat, called a trinucleotide repeat since it adds three new "letters" to the DNA message, causes the resulting protein to fold incorrectly. Proteins are all about folding, it is their three-dimensional shape that gives them their unique function. Imagine if you needed a wrench for a certain repair job, and the manufacturer mistakenly bent the top of the wrench at a 45 degree angle... it would make it very difficult to complete the task at hand. Proteins operate in much the same manner.

Another interesting aspect of repeats is the fact that they have the ability to increase in size from generation to generation. During the production of egg and sperm cells in humans (called meiosis), similar chromosomes line up with one another. The repeats can cause a misalignment, which can increase the size of the repeat. More repeats means a more severe form of the disorder. That is why everyone with fragile X does not have the same symptoms (what us geneticists call a phenotype).

Since Fragile X is on one of the sex-chromosomes, males (who are XY) are definitely more susceptible to its effects, since females (XX) at least have the chance to have a second, good copy of the chromosome. Fragile X syndrome can result in both mental retardation and a form of autism. In fact the recent attention to autism has resulted in some interesting discoveries about fragile X, specifically its relationship with a group of receptors on the cells in the brain called mGluR5. Identification of a receptor is a big deal, since drugs can be developed to interact directly with the receptor. Individuals with fragile-X also sometimes display aggressive behavior, but that is most likely believed to be a secondary result of the disease, probably brought on by speech difficulties, frustration, and anxiety - complications of the effects of mental retardation.

While drug studies are promising, a "repair" of fragile X is unlikely. Since the repeats in fragile X can be very large (200+ copies sometimes) it is unlikely, at least in 2008, that the defect could be repaired using any form of biotechnology, including gene therapy. Furthermore, since the gene product, FMRP, has already caused problems in the cells, it would probably not be possible to reverse the influence on the person. We should be able to treat the symptoms, and it appears that we are getting better at understanding how to do this, but this may be a good example of where our genetic limitation lie.

Friday, September 19, 2008

What is LRRK2?

The recent announcement that Sergey Brin, the multibillionaire co-founder of Google, has discovered that he possesses a genetic mutation that predisposes him to a form of Parkinson's disease has resulted in multiple stories in the news on the "genetic basis" of Parkinson's and the candidate gene LRRK2.

But what exactly is LRRK2? The fact that we now have names for so many of these genes signifies one of the true advances in modern medicine - the fact that we actually know the location, but not necessarily the function, of most genes in humans. But we often forget that these genes themselves are very interesting. LRRK2 stands for leucine-rich repeat kinase 2, which means about nothing to most people. This means that the gene encodes for a protein that has within it a leucine-rich regions, and some sort of kinase function. Still mean nothing? Well, leucine-rich regions tend to be associated with proteins that interact with one another. This is common in many metabolic pathways. In fact, we know that the dardarin protein (the protein encoded for by LRRK2) is actively involved in the mitochondria of the cell - the energy powerhouses that burn carbohydrate fuel to produce energy. And the term kinase indicates that this protein is basically a form of cellular "on-off' switch. Kinases add phosphates to other molecules, effectively turning them on or off. So dardarin turns on and off other proteins.

So what does this tell us? Well, by dissecting the name we can see that this gene, and its gene product (the dardarin protein) are most likely a component of a much larger, protein activation pathway. From a cellular perspective, these pathways can be, and usually are, very complex, with defects at many locations possible. Any of these defects may cause Parkinson's. The disease may also be caused by mutations in genes that have nothing to do with dardarin or LRRK2. So, it is unlikely that the discovery of Mr Brin's mutation will be the silver bullet in the fight against Parkinson's disease. Mutations in this gene account for only a small percentage of Parkinson's cases. However, Mr Brin's announcement will serve to increase awareness, and hopefully funding, of research to better understand the chemical pathways that LRRK2 is part of. But we can add dardarin to the diseasome, or those proteins that are known to cause disease. And once we understand the function, we may be able to start talking about gene therapy and drug development.

Sunday, September 14, 2008

The Reality of Race

What really makes us different? As the father of two young children, I am constantly amazed at how my children begin to distinguish themselves from others in their class. At a very young age, they barely recognized that not all people were the same, and what differences they did note were more of a curiosity to them than a type of distinction.

Now, however, as they exit middle school, they are well aware that some people are "different" from them. Sure, some of it is their social environment — we all know that middle schools are not the model of social integration. But as a scientist, I always have been intrigued by the apparent need to define ourselves as unique, even when it is clear from a scientific perspective that the majority of these differences are due to very minor variations in our genetic makeup.

Despite the ongoing "nature versus nurture" argument between the social scientists and geneticists, as scientists we always have suspected that our underlying differences would have to be controlled by genetics and the biochemical pathways that those genes regulate. While we now recognize that the environment does play a role in gene expression, and few of us believe that we are genetic automatons, barely a week goes by when we are not made aware of a new discovery on the genetic basis of a behavior or a disease. Genes control phenotypes. If race is such an important aspect of our society, as is clearly demonstrated by the latest political cycle, why has it taken us so long to really take a good look at the "phenotype" of race, and determine whether race is genetic?

Over the past several years there have been a number of articles that address the concept of race. One of my favorites is "Does Race Exist?" by Michael Bamshad and Steve Olson, from the Nov. 10, 2003, issue of Scientific American. I make this a required reading article for all of my science classes, from non-scientists to future geneticists.

The basic premise of this article is that the pigmentation level of an individual's skin is a poor criteria to use to identify them as belonging to a specific race, and that the use of these phenotypic races in medicine is bound to create problems.

The authors give an example of African Americans, who are typically identified as being of African descent. However, Africa is not home to a group of genetically identical individuals. Sub-Saharan Africans are genetically different from those from South Africa and the Mediterranean regions.

What is really important is how these populations of humans have historically adapted to selective forces including disease and the environment. Groups that have responded to similar selective forces are more correctly classified as a "race" than those with similar skin colors.

A recent NewScientist article, "Watson vs Venter: the loser is race-based medicine," brings two of biotech's big names to center stage on the discussion of race. James Watson and Craig Venter have made their genomes available publically. (For details see Venter and Watson.)

As Ewen Callaway reports in the article, an analysis of Watson's genome indicates that Watson, a phenotypic Caucasian, possesses a number of mutations that are found most commonly in populations from East Asia.

What this means is that Watson's doctor may prescribe him codeine or antidepressant drugs based upon his Caucasian phenotype, without realizing that at the metabolic level, Watson's cells are operating as if he is Asian.

The same thing is probably happening in each of us. Now that the two big boys, and their associated financial clout, are involved in the discussion, maybe we can really start to talk about what race means.

I, for one, am encouraged that these discussions are starting to gain momentum. At a time when humanity appears to be obsessed in establishing differences based upon race, sexual orientation, ethnicity and religious preference, it is promising to see that the scientific community is working to dispel these notions.

Research into the genetic basis of race needs to continue, not only for the development of new drugs, but to break down society's stereotypes of race. We need to recognize that while the person next to us may look different than we do, he or she may have more in common with us as an individual than a person of our perceived "race." I have a hard time seeing how anything negative can come from this realization.

This entry was originally published as "The Differences Within Us: The Latest Scientific Discussions on Race and Medicine" in the Sept 11, 2008 volume of Bioworld Perspectives. It is reprinted here by permission of AHC Media.

Saturday, September 6, 2008

Synthetic Life Makes Synthetic Proteins

The genetic code is the metabolic instructions by which the genetic information in the DNA is translated into a protein. The fact that almost all organisms use the same code is prime evidence that all life is related in its evolutionary past. The code is considered to be "conserved" and "universal". Of course, the concept of universality may be challenged by exobiology's explorations of Mars, Europa, and Titan, but the conservative nature of the genetic code, with the exception of a few Archaebacteria, has always been a cornerstone of biological science.

But the reality of course is that the Genetic Code is like the Cobal language of computer science. The Genetic Code is old (over 3.5 billion years). Of course life on this planet is not going to update the genetic code anytime soon - it is thriving using the old code, but evolution is a weird thing, if something better comes along, and a mechanism to adapt to that change exists, the out with the old and in with the new. Until recently it appeared to be metabolically impossible to "update" the code. But one species, Homo sapiens, may have discovered a way to fast-track the process.

The basic tenants of the genetic code is that the information coming from the DNA, in the form of messenger RNA, is "read" by a ribosome three units (also called a codon) at a time. Each codon codes for an amino acid, the building blocks of a protein. Proteins are the workhorses of the cell - everything depends on them. In other words, genes code for proteins. While we have had the ability to change genes for some time, using recombinant DNA technology and genetic engineering, until recently we were always confined to the use of the same old programming language.

Earlier this year, independent teams of researchers at Harvard University and the University of Cambridge have found ways to alter not only the genetic code, but also the cellular machinery responsible for deciphering the code - the ribosome. (see Synthetic biology: Rewriting the code for life by Linda Geddes, 2008). This process is called synthetic biology, and due to the efforts of biotech giants such as Craig Venter, this is no longer science fiction. We now have at our fingertips the technology to create new forms of life that are designed for specific missions and environments.

These advances open up unbelievable possibilities, and the potential for unimaginable nightmares. It may soon be possible to manufacture proteins that were not possible from a biochemical perspective just a few years ago. This could create new drugs that could finally eradicate some of our specie's biggest problems, such as cancer and HIV. It could also allow us to develop plants that tolerate salt water, or grow on toxic waste. A new programming language means endless possibilities. It also could spell our demise as a species. After all, the evolutionary history of life on this planet tells us that if something better comes along, the old is replaced... even if it is us. Let us not be so egocentric to think that we are special from an evolutionary perspective. Unless of course, you believe that our purpose on Earth is to generate our own successors.

Tuesday, September 2, 2008

Nondisclosure Agreements for First Dates

Michael Creighton's latest thriller, Next, presents all sorts of what-if scenarios for the genetic community. While most of us will not have to deal with foul-mouthed orangutans or smart-ass parrots, a recent report published in the Proceedings of the National Academy of Sciences suggests that there may be a genetic factor contributing to fear of commitment in males. As reported today by the BBC ("Commitment phobes can blame genes", Sept 2, 2008), this gene is called AVPR1A. Males with a certain allele for this gene (allele 334)have an aversion to commitment, and are less likely to have happy, fulfilled marriages.

Maybe this is not a surprise...but it could be a problem for some males. In a Creighton-world scenario, a male goes out for a date with an attractive women. As he excuses himself to go use the restroom, the woman quietly swabs the inside of his glass, removing a few epithelial cells. She then sends these off to a genetic screening lab where she finds out that the male possesses two copies of AVPR1A allele 334. The next day she ends the relationship and then publishes his name on her blog to warn her friends that he is a hopeless cause. If you think that these tests do not exist - click here.

Why would she do this? Because there are evolutionary differences between the ways that men and women view relationships. Like it or not, in the animal kingdom (to which humans belong), women often form long-term relationships for the purpose of rearing young. Men, on the other hand, are more likely to seek multiple, short-term relationships. So back to humans.... why should the female invest valuable time and energy in a relationship that is genetically bound for failure? No longer do women have to contemplate whether he will "change" - the genetic evidence will tell them. Anyone else hear warning sirens?

So guys, the next time you go out on that first date, make sure that you have your partner sign a non-disclosure agreement stating that any genetic information that she obtains as a result of your date is to remain your legal property unless you consent to its release. Of course, that type of conversation will probably also stop you from getting a second date, but at least your little genetic secret may remain private.

Tuesday, August 19, 2008

Hockey Players and the Minority Report

What if society could identify aggressive behavior in individuals before a criminal act was committed? Sound a little like the Tom Cruise movie Minority Report (2002)?,well it should. Researchers at Brock University in Canada have recently completed a study of hockey players and found out that the aggressive tendencies of these individuals is associated with a higher width-to-height ratio of the face. This increased ratio is linked to higher levels of testosterone, which is linked to aggressiveness.

The problem with this research is that someone may attempt to pre-identify a criminal based upon an inherited characteristic. Sounds good? Well, maybe, if the study is done right. Not too long ago, studies of Jacob's syndrome, males with an extra Y chromosome (XYY), predicted that since these males had an extra Y chromosome, that they should have higher testosterone levels and be more aggressive than "normal" (XY) males. Unfortunately, this is not entirely true. These males do not typically have high testosterone levels, and although they may show higher levels of aggression, this is usually attributed to learning and social problems as a result of the syndrome. These, of course, are treatable with proper identification.

So back the minority report. Should I be keeping an eye on my block-headed neighbor for signs of criminal intent based upon this study. Probably not. Another explanation may be that people with different width-to-height ratio of the face may prefer to play hockey rather than other sports. Who knows, maybe this gives them advantage when being knocked in the head by a stick, or maybe low width-to-height ratio people are selected against in tryouts. In either case, lets not make Minority Report a reality. People should be prosecuted for their actions, not their genetics.

Thursday, July 24, 2008

Cell Phones and Cancer - Round X

As reported on CNN (Cancer expert warns employees on cell phones, 7/23/2008), Dr Herberman, director of the University of Pittsburgh Cancer Institute, has advised against the use of cell phones by employees, citing that it may possibly cause cancer. Here we go again.....

This type of grandstanding by a official should not be tolerated by the academic, medical or scientific communities. It does nothing but confuse the general public and further degrade the reports of legitimate scientists (which Dr. Herberman is suppose to represent!). Reports like this one often go viral over the web, and most often get distorted in many ways. I predict that the National Enquirer will soon start to blame all of the celebrity problems in the news on the use of cell phones. If I was on the staff of this Institute, I would be asking some tough questions of my leadership.

Is it possible that the use of cell phones may increase the risk of certain types of cancer? There is always a possibility - even though multiple published reports have discounted this idea. There may be physiological and genetic factors that predispose some individuals to certain forms of cancer, and these people may use cell phones, but that does not really mean that the cell phone caused the cancer. Should additional studies be performed? ..... maybe, especially if it covers some area of study that has been neglected in a previous study, including the effects on youn brains. Herberman contends that we can't wait for the scientific process to examine the link..... and he is the head of a major scientific cancer institute? Something doesn't sound right.

I wonder if Dr Herberman drives to work in a car..... after all, we know for certain that cars kill over 40,000 Americans per year, and that the emissions from automobiles are killing additional thousands per year (as reported by the World Health Organization)....but I don't hear any outcry about that from Dr Herberman.

For a more detailed report - see the AP report "Pittsburgh cancer center warns of cell phone risks"

Tuesday, July 22, 2008

I am Legend - The Sequel?

There has recently been another documented case of the Hendra virus in Australia (see Rachel Nowak’s “Could killer horse virus spread amongst humans?” In case you are not familiar with Hendra, it is a respiratory disease virus of horses, and is believed to be found exclusively in Australia. The disease has been known to jump to humans from horses, and there have been a few fatalities, but in general, this virus has not gathered a lot of media attention. What is interesting about this article is that Nowak reports that the new version of the virus may be slightly different than the previous versions. So why is this important?

In general, viruses are very specific in the species, and even the types of cells within a species, that it infects. However, the big problem with viruses is that most viruses have a high mutation rate. This means that the genetic material within the virus, which may be either DNA or RNA, changes at a faster rate. Some of these changes, especially when they are compounded over time, may cause the virus to change some of its proteins, and “recognize” new hosts. By the way, for you diehard creationists out there, these genetic changes are an example of evolution, and viruses have been doing this for millions, if not billions, of years. Some viruses mutate fast, others more slowly. Hendra virus has already done this, as it is appears to be derived from a virus found in fruit bats. Since fruit bats, horses, and us are all mammals, it appears that this virus has a special liking for warm-blooded creatures. For that reason alone, we need to pay attention to this one.

While I am glad to see that magazines, such as New Scientist, are reporting these outbreaks of Hendra virus, I am a little worried about how the general media is going to spin this story. If you remember, not too long ago the media picked up on scientific claims that scientists were predicting that the H5N1, aka “Avian Flu”, would leap to humans from poultry. With the release of “I am Legend”, many people believed that the apocalyptic end of the planet was at hand. When it didn’t happen that summer, or even the next, avian flu quickly faded from people’s minds, even though it has been increasing its range annually.

In fact, I still have friends of mine who claim that this was just another example of scientists blowing things way out of proportion. Some of them even try to use this logic to say that scientists are doing the same thing about climate change. This just shows a complete lack of understanding, and respect, for nature. Nature does not work on our timescale, nor does it even have a timescale. When these viruses mutate, as they have for millions of years, they may just develop the ability to infect a new species. And if that species is us, we are going to really wish that we had paid a little more attention to those over-reacting scientists.

Wednesday, June 18, 2008

Men: The Next Endangered Species?

Men, have you recently had one of those feelings that something was not exactly right? A sense of impending doom? An uneasiness with the state of the world? While it was not exactly front-page news, an article by Nick Lane in the June 7th issue of New Scientist (One Baby, Two Moms) should have all men worried. Lane’s article has to do with the generation of a embryonic cell that is basically a hybrid of three parents. The purpose was to transfer mitochondria from one cell to another to potentially prevent disease. The implications for men in general may be much more severe.

Mitochondria are the powerhouses of your cells. These small internal compartments are where your body converts food, usually carbohydrates, into the energy that runs all cellular processes. They use lots of oxygen in the process. In fact, if it wasn’t for mitochondria, the oxygen that you breathe would be lethal.

Mitochondria are interesting for several other reasons. One is the fact that they really don’t belong to us. If you take a good look at the genetics of the mitochondria you will quickly discover that they closely resemble those of the bacteria. The mitochondrial chromosome is circular, just like those of a bacterium, and the structure of the genes on the chromosome is very similar as well. Creationists absolutely hate mitochondria since they provide strong evidence of a major evolutionary event (over 600 million years ago) in the formation of modern cells. Each of our cells contains the remnants of a bacterial infestation hundreds of millions of years ago. But that fact has very little to do with the extinction of males.

What is more important is that we get our mitochondria from our mother. When a sperm cell fertilizes an egg, only the mitochondria in the egg survive. Thus, the mitochondria in my cells are all derived from my mother, who in turn got them from her mother, etc, etc. In fact, our mitochondria provide a history of our heritage. (For excellent coverage of this topic, read Brian Sykes book The Seven Daughters of Eve). But there is a flaw in this process. If there is a defect in a woman’s mitochondria, then she will pass that defect on to her offspring. Since the male doesn’t contribute mitochondria, then there is no chance of getting a “normal” mitochondria from the male. Mitochondria disorders are associated with a number of neurological disorders. Women with a history of these disorders have always been concerned about reproduction.

To bypass this problem, scientists have recently developed a procedure to produce embryos from three parents – two females and one male. This process allows a woman with a known mitochondrial disorder to produce a healthy embryo by using her DNA, mitochondria from another woman, and DNA from a man. The result is a child with the same genetic make-up as would be produced by any normal fertilization event between a man and a woman, but minus the mitochondrial disorder.

Sounds good right? Well, what this has done is place us one step closer to the ability to combine two eggs to produce an embryo. And once that happens men, there will be little reason to keep us around anymore.

Females reproducing without males is nothing new to the animal world. There are several species can either reproduce without males (called parthenogenesis). But until recently, it appeared that males were absolutely necessary for reproduction in mammals. There are several important genetic reasons for this, and the information in Nick Lane’s article does not necessarily indicate that men are doomed – yet. But it does indicate that scientists have overcome another hurdle in their ability to manipulate cells. Soon, perhaps sooner than we think, it will be possible to merge two eggs to form a zygote.

With the news being presented in this article, men are one step closer to joining the dodo bird and passenger pigeons. Author Bryan Sykes has already foretold this in another of his books - Adam’s Curse: A Future Without Men. This should be required reading for all men. For now we are one step closer to that reality. And if the guy at the top of this post is an endangered species… in general are doomed.

Friday, June 6, 2008

The Latest Evolution of the -Omes: The Diseasome Comes to Life

In 1988 if you had told most scientists that the human genome would be sequenced within 20 years, and that the resulting genome would turn out to be the least complicated of the –omes, most of them (including this one) would have said that you had been reading too much science fiction.

I distinctly remember discussions in graduate school about how the human genome probably contained around 150,000 genes. As the years progressed, techniques improved and research continued ... and the size of the human genome began to collapse quickly. At one point I remember hearing a colleague comment on how humans appeared to be "de-evolving" at a record pace! By the year 2000 the human genome had shrunk to around 50,000 genes, and over the next eight years it continued to contract. Recent estimates place the number of genes at around 24,000–30,000.

What had happened was not some major evolutionary genomic constriction event; rather, it was a greater understanding of how genes interacted and were processed by the metabolic machinery of the cell. Scientists began to think that it was not the genes themselves that were important; it might be the gene products that truly mattered.

For many molecular biologists, and probably most of the biotechnology community, the genome turned out to be somewhat of a bust. A disease is a phenotype, an outward portrayal of a trait, which in the case of most diseases has an underlying cause in the genome, but not in all cases. Creutzfeldt-Jakob disease is a nice example of a condition that is caused not by a defect in a gene (although there is some suggestion of genetic susceptibility), but rather by a malfunctioning protein called a prion. In fact, most diseases are caused by protein-related problems. Thus, in order to understand human disease it was necessary to take a good look at the proteome, or the sum of the proteins within a cell.

The size of the proteome appears to be even more elusive than the size of the genome. Estimates range from between 90,000 to more than 400,000 proteins in the human proteome. Of course this number is dependent on a number of items, including cell type, influence of external stimuli, cell age, nutritional state, etc. The proteome is the cell's response to its environment, and therefore it is expected that it will fluctuate depending on the needs of the cell.

So while some still work to identify the entire proteome, attention has shifted to what the proteome can tell us about the health of a cell. To do that, it was necessary to understand interactions within the proteome. This is called the interactome and it encompasses the study of all interactions at the molecular level within cells. The interactome is based primarily on protein-protein interactions. This led to amazing breakthroughs in systems biology, which integrated biochemistry, molecular genetics and cell biology to more fully understand how cells work.

Something very interesting occurred at this point. When studying protein interactions it is often useful to go back and identify the genes that code for each protein. Advances in biotech have made this a relatively easy process, and it was only a matter of time before scientists began to uncover some intriguing connections. In a New York Times article by Andrew Pollack, the author interviews scientists who have used studies of the proteome and interactome to reveal genes common to both heart attacks and muscular dystrophy — two seemingly unrelated conditions.

In other words, molecular science has come full circle. An understanding of the genome is once again important, but so is an understanding of the interactome and proteome. Together, these items are sometimes called the diseasome. The diseasome represents the latest evolution of the -ome; it fully integrates all information to understand factors that may cause a disease.

If you are having a hard time visualizing the diseasome, then a quick visit to an interactive graphic on a portion of the diseasome prepared by The New York Times will help immensely. If you notice, there are connections in this diagram that seem to be impossible if you think only about the disease, such as genes linking myocardial infarctions and Alzheimer's disease. But if you step back from the disease for a second, and integrate the information, it starts to make sense. At the cellular level, metabolic activities are directed by genes and proteins interacting in complex manners. Since there are a limited number of genes and proteins, but a seemingly unlimited number of diseases, then there must be common factors that we have previously missed.

So what does all of this mean? The ability to visualize these interactions may allow medical researchers to develop innovative methods of detecting and treating disease states. Some, such as Dr. Albert-László Barabási at The New England Journal of Medicine and Northeastern University, have called this network medicine.

In the very near future, as more of these interactions are mapped out, doctors may begin to prescribe unique combinations of drugs that would have not even been considered 10, or even five, years ago.

Diseases that previously were thought to be too complex to cure, such as muscular dystrophy and diabetes, may very soon be things of the past.

Note: this article first appeared in the June 5, 2008 issue of BioWorld Perspectives, and is reproduced here by permission of AHC Media, LLC

Monday, April 28, 2008

It May Not Pay to be Smart...If You Are a Fly

It pays be to smart.....doesn't it? Many of us struggled through years of undergraduate and graduate school just to get an upper-hand in the great game of life. But now, a new research article in the journal Evolution suggests that, at least for flies, being smart is going to cost you... in lifespan.

Researchers at the University of Lausanne bred flies that were "smarter" in responding to specific scents than other flies. When they took at look at the lifespan of these flies they realized that the "smart" flies lived about 15% less time than the , well, "not as smart" flies.

Drosophila are often used as model organisms for a variety of genetic studies. This study is important in that it may help shed some light on the "costs" of intelligence. By costs I mean what the organism has to give up in order to develop intelligence, and this is something that we really need to know if we are going to ever figure out how complex intelligence evolved on this planet. However, lets make something clear... these were not smart flies. Flies really aren't very bright, I know, I breed them. They are like fish in a tank... pretty to look at, but not much going on upstairs. So although we can use fruit flies for a variety of purposes, let us not give them credit for being smart.

What I worry about is what will happen when a sound-bite of this information gets out. We already have a problem keeping kids in school - telling them that straight A's will cost them 10 years of their life... well, that would be a mistake. Someone, somewhere, is going to use this information to justify dropping out of school and smoking 2 packs a day.... just watch.

Sunday, April 13, 2008

My Friend, E. coli

While as a geneticist my vote would go to Drosophila melanogaster as the greatest organism of all time, I do recognize that Escherichia coli is probably one of the most beloved organisms of the biomedical research community. This versatile little microbe can be found in teaching and research labs from high schools to research institutions and large biomedical facilities. We probably know more about E. coli than almost any other organism on the planet, including ourselves. Many of the advances in medicine and drug development would probably not be possible if it were not for this wonderfully versatile little bacteria. But, as we are all aware, E. coli has a dark side.

The March 24 issue of New Scientist features an article ("Mystery Food Poisoning Traced to Salads") which presents statistics on the increase in the rate of food poisoning associated with salad greens. While the article does not specifically mention E. coli, if you asked the common person on the street what was causing the food poisoning in spinach and lettuce, most would guess this bacterium. In fact, E. coli is probably the only microbe, or any other organism for that matter, that most people know by its scientific name! Unfortunately, that recognition is not a good one. From baby diapers and water parks in the 1990s to ground beef and salad greens in this decade, E. coli has earned a reputation as a menace.

I have found that most students are surprised to find out that their intestines contain more bacterial cells than there are human cells in their bodies. Most are disgusted by the thought, and some actually pale when I mention that one of the leading organisms is E. coli. I have even had a few ask if they can get antibiotics from the campus health clinic to rid them of these "parasites."

After a brief discussion of why these little creatures are present in our system, and the benefits that they provide us by protecting us from harmful bacteria, synthesizing necessary vitamins, and stabilizing our blood glucose levels, most of the students develop a real appreciation for E. coli. From that point we can proceed to discussions on how important it is to keep your intestinal bacteria content by reducing unnecessary use of antibiotics and consuming plenty of fiber. It is then relatively easy to understand why probiotics, such as yogurt and Acidophilus pills, work as supplements. With a little public relations work, E. coli is transformed from the villain to a misunderstood hero.

Why is any of this important? In the March 1 edition of Science News, science writer Janet Raloff ("Nurturing Our Microbes") presents an intriguing possibility that someday it may be possible to reprogram our natural flora of microbes to combat disease. She first discusses how probiotic supplements may be used to increase the efficiency of intestinal bacteria in enhancing our immune system, by increasing the absorption of nutrients such as calcium and by regulating weight. Raloff then presents comments by Jeremy Nicholson of the Imperial College in London, who said that future drug therapies might one day be directed at the bacterial inhabitants of the intestinal system.

As a researcher, I think that is an important advance for medicine. We all know of the problems that have plagued large-scale implementation of gene therapy. Given the number of bacteria in the lumen of the gut, it should be possible to achieve a higher rate of transformation than is experienced in in vivo eukaryotic cells. Furthermore, by having the bacteria produce the drug of interest, it may be easier to get the drug directly into the bloodstream than traditional oral routes that need to navigate the hostile environment of the stomach.

And since this is an election year, and at least some of the focus appears to be on health care, the use of genetically modified E. coli may reduce the cost of certain medicines, since once transformed the individual would have a constant, renewable source of the drug.

However, before we proceed with the development of drug-producing recombinant bacteria, I would like to make a suggestion. If the drug companies state that they are ready to produce a genetically altered bacterium, especially one named E. coli, the general public is going to have a revolt.

Movies such as I Am Legend have not presented a pretty picture of genetically engineered organisms. Recent public responses to cloned meat, and once again to certain forms of immunizations, reveal that the general public is not convinced that we know what we are doing.

So my suggestion is this — start a public relations campaign on behalf of E. coli. Get E. coli, or its agent, on The Daily Show and Good Morning America. Start thinking about how to spin the benefits of E. coli to an increasingly research-phobic public. Work the media, begin ad campaigns, and most importantly, get the message out to the science teachers to incorporate it into their curriculum. For if we don't, this promising medical advance may be a tremendous waste of money.

Note: this article first appeared in the April 10, 2008 issue of BioWorld Perspectives, and is reproduced here by permission of AHC Media, LLC

Friday, April 4, 2008

Autism in the News

Autism is once again in the news. In the past several weeks news agencies, such as CNN, have brought autism back into public thinking through coverage both on TV and the web. While the news network has done an adequate job of presenting the concerns of parents and the opinions of the scientists, they have done very little to present the basic scientific information about autism. From my perspective, most people are completely confused about autism. In the past, an autistic child was sometimes viewed as the fault of the parents, and in the current round of coverage the disease is sometimes being presented as a result of a medical community which prefers not to face the facts regarding vaccinations. Neither of which is really true. Instead, we need to recognize that autism is a very complicated disorder – and that complicated disorders can take some time to sort out.

First of all, and probably most importantly, autism is most likely not a single disease. Like Alzheimer’s disease and cancer, autism is a term that we have adapted to explain a related group of symptoms, in this case severe communication disorders. Alzheimer’s researchers now distinguish their disease using terms such as “late-onset” and “early-onset”. We need the same approach for autism. We need to develop a common set of classifications for the disease so that we all know what type of autism we are talking about. And these classifications need to be easily understood by the news organizations and general public. No scientific techno-babble please! For those who are trying to understand autism, we need to be able to distinguish the various forms so that we know if the news and the scientific community is talking about a common form or a rare form. Also, since autism is not a single disease, we can’t expect that the disease is caused by the same factors in each case. Which leads me to the second important point – genetics.

Autism is probably what geneticists call a multifactorial, or complex, disorder. What this means is not only is genetics involved, but also environmental factors. Those environmental factors are without doubt chemicals. While the news has been focusing on thimerosal, a chemical additive that was used in many vaccines, the truth is that we live in an increasingly chemical world. Some scientists estimate that we come in contact with over 70,000 man-made chemicals over the course of our lives. We have no idea how many of these chemicals interact with each other. In other words, our cells, and especially the easily influenced cells of a developing child’s nervous system, are being bombarded with a potentially hostile array of chemical compounds. Now, back to the genetics. Many of our genes have minor variations that go unnoticed until the cell is placed in a certain environmental condition. So say for gene X there are 2 variants, lets call them X-1 and X-2. When X-1 is exposed to a certain chemical cocktail, the gene continues to function normally. But when X-2 is exposed to the same group of chemicals, the environment alters the way the gene works, called gene expression by scientists, producing slight changes in the cells. In a complex trait it may be necessary to have many of these gene variants, say X-1, Y-4 and Z-2 acting at the same time to produce a disorder. Sorting out multifactorial complex traits takes time and patience by the scientific community.

So what can we do? As parents and concerned individuals we need to aggressively lobby our elected officials to increase funding to not only study this disease, but to make life better for the increasing number of kids who are being diagnosed with autism. In addition to long-term studies of people with autism, we need to start enrolling pregnant mothers in prenatal studies that examine everything from the genetics of the parents to the types of chemicals that the mother comes into contact with during her pregnancy. Only then will we be able to provide some real answers on what is causing autism, and maybe develop a means of reducing its impact on future generations.

Monday, March 3, 2008

New Hope for Short People???

"Tall people have tall children, and short people have short children." For many this statement summarizes all that needs to be known regarding the relationship between a person’s height and heredity. For geneticists, however, these types of general observations represent an open intellectual challenge, since a more careful observation of the human population reveals that there is considerable variation with regards to height, and that it is possible for tall people to have short children, and vice versa.

A Quantitative And Multifactorial Trait

For years scientists have known that height is a quantitative trait, meaning that the population does not fall into distinct phenotypic classes. Anyone who purchases clothes knows that people are not "tall," "short" or "medium." Instead, height in humans is distributed around a mean value. This form of distribution, or bell-shaped curve, is characteristic of a trait that is under the influence of multiple genes, each one having an additive effect on the phenotype. The more of the
alleles that a person has, the further along the distribution the phenotype is located.

Geneticists also recognize that height is a multifactorial trait. Multifactorial does not mean simply that multiple genes are involved. The term multifactorial indicates that there are both genetic and environmental factors that are contributing to the observed phenotype.

A wonderful illustration of the multifactorial basis of human height is provided by Ricki Lewis in her textbook, Human Genetics, Seventh Edition. Lewis presents two photos of the graduating class of Connecticut Agricultural College, one taken circa 1920, the other in 1997. In both photos, the students were placed into phenotypic classes by height (to the nearest inch). The distribution of both classes follows a distinctive bell-shaped curve characteristic of a quantitative trait. The difference is that the mean height of the 1997 class was much greater than that of the 1920 class. Whereas the tallest individual in 1920 was 5’9", the tallest individual in 1997 was 6’5".

Since it is unlikely that a "tall" mutation has infiltrated the entire graduating class, and therefore the genetic basis of the two populations should be roughly the same, then there must be some other factor involved. Human geneticists and medical professionals say that the overall change in height over the past several decades is primarily due to improvements in human nutrition – an environmental factor. Building on this, geneticists have suggested that human height may be the
result of the interaction of environmental factors with several major genetic mechanisms and a host of minor genes.

Use Of Genome-Wide Association Studies

As a geneticist who has studied quantitative traits in Drosophila, I can testify that one of the hardest problems facing quantitative geneticists is the ability to tease out the influence of major and minor genes on a phenotype. Many methods exist to investigate the contributions of a single gene to a phenotype, but searching for all of the minor contributing genes has remained a relatively difficult task. Recently, a research group led by Timothy Frayling at Peninsula Medical School in Exeter, UK, reported the use of the genome-wide association studies (GWAs)
to identify genes responsible for variations in the height of humans (Nature Genetics, October 2007). The use of association studies in human genetic analysis is nothing new as they have been used with a variety of genetic markers for several decades. However, the use of GWAs in this manner is something significant as it allowed the researchers to look at contributing alleles across the genome, and not simply in the vicinity of candidate genes. This technique should give researchers the ability to identity a greater number of minor genes, or those that make smaller contributions to the phenotype in question. This could prove to be very useful for complex diseases and traits that are under the control of multiple genes.

Breakthroughs In HMGA2

The gene that Frayling’s group identified, HMGA2, is not a new discovery. As the researchers report, it has been known for some time that severe disruptions of this gene can cause drastic changes in the height phenotype (dwarfism and gigantism) of mice. What Frayling was able to show is that certain alleles of this gene are associated with height at specific times during development. Interestingly, the associations indicated that certain alleles are associated with an
increase in height between the ages of 7 and 11 years and persisting into adulthood. This identification of this temporal importance suggests that other genes remain to be identified that play a role earlier in life. But there is also a catch – the gene that is responsible for the added height is also associated with an increased risk of certain types of cancer. The gene product of HMGA2 belongs to a family of proteins that act as DNA-binding proteins, meaning that HMGA2 most likely has a role in the regulation of gene expression. Although HMGA2 is not an oncogene, it has been observed to be overexpressed in certain types of tumors, meaning that while a gene might be a minor gene in one quantitative trait, it may be a major gene for another trait.
With the developing promise of gene therapy might it be someday possible to prevent individuals from being vertically challenged? In today’s world there is always someone who will want to capitalize on a discovery such as this by promising increased height to short people. Though some might see it as an opportunity to change or select the phenotype of an individual, in reality this paper has a far greater significance. The identification of HMGA2’s role in height
is an important breakthrough in the study of complex quantitative traits, and it demonstrates the power of new genome analysis techniques that are coming online. As Frayling and his colleagues suggest, the true power of this technique will be when it is applied to the study of complex diseases.

This article was originally published in BioWorld Perspectives (vol 1 # 46) in November 2007 and is reprinted here by permission from AHC Media LLC.

Monday, February 18, 2008

Fountain of Youth??

Growth hormones are once again in the news. The difference is that this time it is not the debate over the presence of growth hormones in the food supply. Instead, the focus is now over the use of growth hormone supplements. Over the past few months the media has been covering a set of stories regarding human growth hormone, also known as hGH or somatotropin.

The controversy of the Mitchell report and Roger Clemens in professional baseball (although mostly focused on steroid use), admittance by performing artists that they have used somatotropin to look younger, and even Rambo's confession that he not only uses synthetic growth hormones, but also recently tried to illegally transport some into Australia, are just a few of the more recent headlines that have raised public interest in learning more about the use of performance-enhancing growth hormones. And as usual, the public may not be getting the complete story.

Growth Hormones: Fact vs. Fiction

If idols in Hollywood and professional sports are using growth hormones, then why shouldn't we all use human growth hormone supplements? After all, the scientific community presented evidence in 1990 that injections of somatotropin can provide small decreases in body fat and increase muscle mass — neither of which appears to be a bad idea when we are faced with the fact that our population is getting older and heavier. There are claims that it can increase the sex drive and remove wrinkles.

As an aging science writer, that doesn't sound too bad, except that in the back of my head the nagging voice of the scientist in me keeps saying that maybe I should check the facts first.

So what are the facts? Well, the truth is that the biotechnology community is still investigating whether the use of somatotropin really has any of these beneficial effects. The hormone is used clinically to treat complications from HIV, dwarfism in children, and burn victims, but as a performance-enhancer the debate is ongoing.

More recent studies appear to contradict the 1990 report, and the few longer-term projects on the effects of growth hormone supplements in seniors have indicated that use of somatotropin does not provide a significant increase in muscle strength, but it does increase swelling, joint pain and chances of carpal tunnel syndrome. Several researchers are currently looking at whether use of growth hormones increases the rate and spread of certain types of cancers.

Reevaluating Role Models

But really, if an adult wants to take a supplement, should we be concerned? After all, a trip into any pharmacy or grocery store reveals aisle upon aisle of unproven remedies for any number of conditions. One story in general explains why as a society we should not condone the use of somatotropin for reasons other than those approved by the FDA.

In January 2008 Luis Fernando Llosa and L. Jon Wertheim reported in the rather disturbing Sports Illustrated article "Sins of the Father" on the real costs of the use of human growth hormone. The story focused on Corey Gahan, a teen-age in-line skating champion who admitted that he was pressured by his coaches and father into receiving injections of steroids and human growth hormones for the sole purpose of improving athletic performance. The combination was highly successful, and Corey became a national champion in his age class. However, after routine testing Corey was stripped of his titles and banned from additional competition.

The truly sad aspect of this is the fact that both Corey and his father, who served jail time for providing the drugs to Corey, both believed that the only way to be competitive was to take performance-enhancing compounds.

And where did they get this idea? From professional athletes of course — the very ones teen-age athletes put on the pedestal as role models. In other words, society set the standards and the young athletes pay the price. Unfortunate as it may sound, youth look to us as role models.

Too Good to Be True?

There is a real chance that supplements of growth hormone may provide some real medical benefits. Ongoing trials have already hinted that this is the case. But as scientists in the biotech community, we should begin an aggressive campaign of our own to let society know that they need to be patient and wait for all of the evidence to come in before jumping on the somatotropin bandwagon. The medical community should make it clear that they will report all illicit use of their drugs, in any form, since failing to do so seems to send the message that doctors and physicians don't really care about what is done with the medicines that are prescribed.

And let us agree that we will research the long-term effects of growth hormone use before we sell it as the next miracle drug. Our experience should tell us that when something seems too good to be true, it usually is.

Note: this article first appeared in Bioworld Perspectives, (vol 2; #7) on February 14, 2008 and is reprinted here by permission of AHC Media, LLC