Ricochet Science - Life Sciences

Ricochet Science is Moving!!

2009-12-01T21:29:00.002-05:00

As of January 1, 2010, this blog is moving to a new location - ricochetscience.com . In the process we will be evolving to include both pod and video casts, and coverage of sciences other than just genetics.

Please come visit us at our new site after the start of 2010!

ricochetscience.com

Sunbeds as Carcinogens

2009-07-29T09:32:00.004-04:00

Finally some sense has been made about the use of tanning beds. A study by cancer researchers supported by the World Health Organization have determined that the use of tanning beds before the age of 30 increases the risk of developing skin cancer, specifically the deadly form melanoma, by 75%. Although the tanning bed industry has for the most part denied any link between tanning beds and increased rates of skin cancer - from a genetic point of view, it was only a matter of time until the evidence supported what we already knew: Lying inside a metal coffin and being bombarded by radiation is bad for your health.

The bottom line is that UV radiation, in all wavelengths, damages DNA to some degree. Some forms of UV are worse than others, but no wavelength is DNA "friendly". To put it bluntly, UV radiation fries DNA. More scientifically, UV radiation causes small breaks in the DNA molecule and the formation of a chemical structure called a thymine dimer. Thymine dimers represent a special challenge for our DNA repair mechanisms, and although our cells have evolved mechanisms to repair these structures, the changes that the repair generates an unintended detrimental mutation is high. If this mutation occurs in a gene that is responsible for regulating cell growth (or maybe even mitochondria now?), the result can be an out-of-control cell - commonly called cancer.

Of course, the head of the The Sunbed Association disputes the claim, stating that there is no link between responsible use of sunbeds and cancer. Seems like similar statements were made in the 1970s and 1980s with regards to cigarettes. I imagine that the debate will now focus on what constitutes "responsible". But according to this study, the only responsible use would be to lie down in the tanning bed and not turn on the UV light. Anything else is simply inviting an increased risk of death.

For more info - see this article in USAToday

A New Twist in Understanding Cell Division.

2009-07-24T21:09:00.005-04:00

Pop Quiz: What is the role of the mitochondria in a cell?

digest incoming food particles
store DNA
produce ATP
regulate the cell cycle

Until just a few days ago, the only correct answer to this question would have been #3. The mitochondria of a cell are well recognized as the powerhouses of the cell. They are the location where energy-rich nutrients such as carbohydrates and fats are brought in and "burned"in the presence of oxygen to produce the energy (in the form of ATP) to power our cells. It is one of the earliest lessons of any introductory biology course.

However, in a development that is sure to change the way we look at cell biology, it now appears that answer #4 also may be correct. A group of researchers at the National Institutes of Health reported in the July 21, 2009 issue of PNAS that the fusion of the the mitochondria in a cell influences the buildup of a protein called cyclin. This in turn, acts as a control mechanism for the cell to bypass an important checkpoint (G1/S), allowing the cell to divide.

Cyclin is a form of protein "clock" within a cell. Its job is relatively simple, as cyclin levels accumulate in the cell, it overcomes a series of thresholds that tell the cell to undergo important activities. One of these activities is the cell cycle. The cell cycle is a type of cell "day". At specific points in the cycle the cell undergoes DNA replication and specific activities to prepare for cell division. These activities are regulated by special proteins called checkpoint proteins. You should be very interested in these checkpoint proteins - their job is to ensure that the cell does not divide unless it needs to, since unrestricted cell growth is called cancer. There are two specific classes of these proteins, proto-oncogenes and tumor supressor genes. Until earlier this week, they were the primary focus of most research dedicated to understanding the cell cycle.

What the NIH team reported is that just prior to one of these checkpoints (G1/S) is that the mitochondria form an unusual tubular network in the cell. The images from their paper show a network of mitochodnria that is reminiscent of a map of a subway line in a major city. The authors then show that the presence of this network is correlated to a increase in a form of cyclin that is known to be a major key in overcoming the G1/S checkpoint, allowing the cell to duplicate its DNA in preparation for cell division.

Why should we be interested in this? First of all, because it demonstrates that by looking in unconventional areas, we can find new clues as to how cell function. Until earlier this week, no one would have answered #4 in the above quiz. But more importantly, scientists who study cancer genetics and biochemistry can now look for relationships between these mitochondria and unregulated cell growth, which should, eventually, lead to new insights on how to battle some forms of cancer.

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Click here to access the article in PNAS

Solutions for the Higher Education Financial Quagmire

2009-05-29T08:23:00.002-04:00

This has not been a good year for higher education. Economic downturns traditionally benefit the educational community by providing a surge of displaced workers to fill the classrooms, but the severity of the current economic situation actually has had a negative effect on campuses across the U.S. While people are returning to higher education, the financial mess on Wall Street has crippled the financial backbone of academia. Across the country, state budgets are in crisis.

In my own backyard, for example, the University System of North Carolina experienced a 5.8 percent reduction in funding in 2008-2009, and the North Carolina state budget is facing a $3.4 billion shortfall for 2009-2010. In addition to budget cuts, the General Assembly enacted a 7 percent reversion in the budgets of higher education — the new name for supplemental budget cuts.

On a more individual basis, since this recession directly involves the financial sector, people are having a hard time securing the funding to return to school, and scholarships and grants are reducing their support as their endowments struggle. Somehow, we have become accustomed to this type of news, with many wondering how any good can come out of this situation.

The Bright Side of Budget Woes
The budgetary quagmire facing academia often is viewed as an obstacle to program and curriculum development. But this actually may be the event that finally catalyzes the blending of higher education and industry.

Across academia there always has been a rather small minority that actively has promoted and fostered direct interactions with the corporate world, not just in the form of grants, but in direct collaborations in research activities and the training of skilled workers to satisfy the needs of industry. Even though the current economic woes also are influencing the private sector, the time may be ideal for a revolution in the way that academia and industry (including big pharma) interact.

We are beginning to see that happen already. At Appalachian State, my home institution, the faculty is actively encouraged to develop partnerships with both the private and government sectors. Within the past few years, long-standing ultra-conservative policies regarding copyrights and ownership of patents have been discarded in favor of more liberal policies that promote technology transfer and cooperative agreements with industry.

The Ethics of Industry-Academic Collaborations
We do, however, need to get a handle on the ethics of these new relationships. In countless committees on college campuses, faculty and administrators are questioning whether these new relationships are in the best interests of the students. As is always the case, a few bad cases can upset years of progress. An excellent example of how ethical problems can cause havoc in an academic program is at Harvard Medical School. A March 2 article in The New York Times outlines Harvard's problems with both faculty and administrative personnel receiving financial support for their research from the pharmaceutical industry. In this case, individuals at Harvard are accused of placing their personal interests over those of professional interests. Even though the faculty and administration at Harvard had disclosed that they were working as consultants to private industry, the students' perception was that the faculty was using these relationships to influence the students' views on certain drugs. While the matter is still being debated at Harvard, it does show that potential problems exist.

Of course, the overall issue is one of transparency. Most of us recognize that transparency is the key to an effective workplace. When all issues are on the table and open to discussion, people feel more comfortable with their environment and their leaders. This type of change has been slow to develop on college campuses, where the authoritarian role of professors and administrators resembles a form of medieval caste system. Most institutions, including Harvard, fail the transparency test — but not all. As pointed out in the article, the University of Pennsylvania, Stanford and Columbia have developed more transparent reporting systems and have received high grades for their achievements.

Promoting Collaborations Through Peer Review
There is another solution, and one that is deeply embedded in the scientific process. The scientific community, both academic and private, prides itself on the peer review process. With regards to research, review by one's peers is considered to be the benchmark of ensuring academic integrity.

What is needed in order to ensure that academic-industry relationships are handled ethically is an adaptation of the peer review process in academic-biopharma partnerships. Simply put, faculty must disclose their relationships to a community of peers, including representatives from industry. Since we are dealing with finances, these peer review committees should be inter-institutional, further compelling an environment of transparency in higher education.

This process will ensure that transparency is maintained, and it will promote the interactions of academia and big pharma. Furthermore, it will help encourage the interaction of academia with the biopharma community, which may result in an influx of much-needed capital into an increasingly bankrupt educational system. These are the types of partnerships that higher education, the industry, and even more importantly, the students, desperately need.

This article was first published in BioWorld Perspectives (May 28, 2009 vol 3 #21) by AHC Media and reproduced here by permission.

Fighting HIV Without Traditional Vaccines

2009-05-20T19:29:00.002-04:00

Why can't scientists just develop a universal vaccine against HIV and the swine flu? Is it because the biopharm industry wants to make money each year off of a new vaccine?

The answer to the second question is a definite "no", but the answer to the first question is far more complicated....

The problem is that HIV, and in fact many viruses, do not play fair. Viruses, although not technically "alive", evolve over time. One way that viruses evolve is by changing the protein structure of their outer protein coat. This protein coat is responsible for the majority of the properties of a virus - for example what species and types of cell in infects. In viruses, the evolutionary rate of change is higher than that of living organisms, for several reasons, including the fact that viruses lack DNA repair mechanisms. This means that they accumulate mutations faster, and often these mutations change the outer structure of the virus. Since vaccines are prepared using purified outer proteins of a virus, you can see how as viruses evolve they make previous vaccines ineffective. Such is often the case in the flu vaccine, where the yearly vaccines are prepared from the previous year's flu viruses. Vaccines for HIV has so far met limited success, and epidemiologists balk at the idea of putting a vaccine on the market which would make people think that they are safe. Furthermore, HIV belongs to a class of viruses called the retroviruses, an especially nasty sub-set of viruses that accumulate mutations faster than most.

Vaccines, when introduced into the body, cause the immune system to target specific cells and proteins for destruction. This is called the specific immune response, and one of the ways that it works is to produce antibodies against the invading virus. Unfortunately, we all do not generate the same antibodies, meaning that a vaccine in one person might not have the same result as in another. Coupled with the high mutation rates of viruses, this causes real problems in developing a population-wide vaccine for highly mutable viruses.

But what if we could bypass the whole antibody-generation step and instead introduce virus-specific antibodies into the body. These antibodies could be designed to target a specific type of virus, and would actively recruit the cells of our immune system to destroy the virus before it caused significant damage. This type of procedure has just been reported for HIV-type infections in primates, and the initial results suggest that it might hold promise. And not only for HIV, but also for viruses such as H1H1 (swine flu) and H5N1 (avian flu). Both of these are now in the human population, and the development of an effective vaccine against them both is not soon forthcoming, so adding a new technique to our anti-viral arsenal is well advised.

For more information - see Jon Cohen's article in ScienceNow
"Designer Antibodies Derail Monkey AIDS Virus"

Say Goodbye to the Printed Textbook....

2009-05-17T09:40:00.001-04:00

I remember distinctly lugging a backpack of textbooks across the frozen tundra of Michigan State University in January. On many occasions, the weight of the backpack was enough to send me skidding out of control on the ice. I hated dragging those books around, but my professors all told me that I had to have a copy of the textbook in class every day (still not really sure why on that one!).

Electronic textbooks have been around for a while, and while the technology has improved immensely from the days of simple pdf files to the newer, more interactive, formats, all have required a computer to access, making the portability of these texts still a little of a hassle. The release of the new e-Readers, such as Amazon's Kindle and Sony's Reader, have created a new interest in downloadable eBooks. For half the price of a printed book, and the ability to download the material without being connected to a computer, these devices have already proven their worth to an increasing audience of book fans.

The major drawback of these devices has been that they are black and white. This simple fact has inhibited the use of the e-Readers for science textbooks, which rely heavily on the use of color graphics. However, E-Ink, the company that makes the electronic paper that powers the e-Readers, has recently announced that it is preparing to launch a color-version of its e-paper. If so, then the door is finally open for the offering of college science textbooks on the e-Readers.

Despite the fact that professors say that a textbook is invaluable, most educators know that students do not read the book and prefer to get their information from electronic sources. Given the size of some textbooks (400+ pages is the norm for an intro biology text), and its lack of interactivity, there can be little doubt as to why student's overall despise textbooks. This generation of students is looking for alternatives, and E-Ink's improvement of the e-paper may be exactly what spells the final demise of the textbook.

The professors will grumble (they always do), but the reality is that once publishers start offering e-Reader versions of their textbooks, we will finally see the beginning of the end of the printed textbook. As a professor and lifelong student, I for one will be glad to see it happen.

New Evidence for the RNA World

2009-05-16T09:53:00.004-04:00

Every instructor of an introductory biology class is faced with a dilema to present to their class. While we know that DNA is the genetic material of all living organisms (except some viruses - but most do not consider them as "living"), it appears to have been absent from the early Earth. So what was the original genetic material? And, more importantly, do we have any evidence to support this hypothesis?

Before we look at the alternatives, was wasn't DNA the original genetic material on the planet? One main reason, of course, is its complexity, and the fact that DNA requires a host of proteins and enzymes to assemble and copy itself. These enzymes are encoded within the DNA, so that leaves us with a "chicken and egg" scenario. The DNA molecule itself lacks any catalytic abilities - meaning that it does not conduct any chemical reactions. It is like the hard-drive of your computer - pretty much useless without a host of assistants to get the information in and out.

For some time scientists have recognized that a second form of nucleic acid, RNA, is the solution to these problems. RNA is a much simpler molecule. It is usually short and only consists of a single-strand of nucleotides. More importantly, RNA molecules can themselves act an enzymes. This type of RNA is called a ribozyme, and its activity appears to solve many of hurdles faced by the early genetic material. The fact that RNA may have been the earliest form of genetic material is called the RNA world hypothesis.

There has been only been one real problem with the RNA world hypothesis. How did the individual components, called nucleotides, of the RNA molecule self-assemble. Many explanations have been proposed, but finally, due to the activities of a group of researchers at the University of Manchester, we are one step closer to understanding. Dr John Sutherland, a chemist has demonstrated a series of chemcial reactions that can occur naturally to form the nucleotides of RNA. This could be a very important advance in the life sciences - previously we have known how to form the nucleotides synthetically (i.e, in a lab), but not under natural conditions.

Now here is where we can link astrobiology (also called exobiology) and genetics together. We are currently exploring Mars for life, and will soon we taking a good look at both Europa and Titan (moons of Jupiter and Saturn, respectively). While it is useful to look for life as we know it - what would be more interesting would be to tart to look for proto-life, molecules that are self-assembling and replicating. Using Sutherland's data, we should be taking a good look at these locations of evidence of RNA-building blocks. By doing so we can understand more about how life first evolved on our planet.

For more on Sutherland's discoveries - see the NY Times article by Nicolas Wade - "Chemist Shows How RNA Can Be The Starting Point for Life"

The Swine Flu "Pandemic"

2009-05-03T19:53:00.004-04:00

Welcome to the new world of medical sensationalism. The recent "outbreak" of the H1N1 virus, aka "swine flu" has provided some of the major news networks with the ultimate story. Scare the public and increase ratings, it worked with terrorism, and now it appears to be working with the swine flu pandemic. From pictures of Dr. Gupta, CNN's medical authority, wearing a worried look and a face mask, to Vice-President Biden's gaff about why all Americans should cease flying immediately, the American people are being fed misinformation on H1N1 at an alarming rate. And they are scared. Airline stocks are plummeting, people are avoiding pork, and sales of surgical masks are increasing exponentially. In Vermont, the National Gaurd is escorting deliveries of anti-viral medicines to hospitals. And, of course, the religious crazies are out predicting the "end of days".

Every day we are reminded of the swine flu death toll. For example, on today's CNN page (May 3, 2009), there is a headline article stating that "Confirmed Cases of H1N1 Virus Approach 900". It is important to realize that 900 deaths, while seemingly significant, really is not. Cancer kills over 440,000 Americans per year, or about 1200 a day. Over 9000 Americans, 24 each day, die from contaminants in the food that we eat. In fact, 900 deaths worldwide represents about 0.00013% of the world's population. This is a nasty little virus, with some interesting genetics (see tomorrow's post!), but it is not yet a global killer. And due to some rather quick work by scientists, we already know more about this virus than most.

So why the panic? Mostly because people do not understand the jargon of the people who study infectious diseases. Yes, there is a pandemic... but it is important to recognize what the word pandemic really means. An epidemic is an outbreak of a disease in a localized population, while a pandemic simply means that the epidemic has moved into neighboring populations. In today's world, most epidemics, and all flu outbreaks, go pandemic quickly. A pandemic is not Armageddon, it is simply a widespread outbreak of a disease.

Some people will say that the news networks are just keeping people informed. But the reality is that this bout of swine flu is going to fade rather quickly as summer progresses, and with this fading will be the attention of the American people. But, unfortunately, the virus will be back, and it could return with a vengeance. But due to the actions of the news networks, we are now in the "boy who cried wolf" syndrome. When this virus, or one of its close relatives returns, most people will ignore the advice to get a vaccine, thinking that this is just another "news story", and not a real threat. After all, they have already survived the "threats" from avian and swine flu, how bad can it get? The answer is, very bad indeed. Viruses are patient little objects, and a few seasons of low activity often preclude a true outbreak in a population. H1N1 may not be bad this year, but if it mutates over the summer, we could have problems next year if we don't prepare now by planning ahead and funding the agencies that work to protect us from infectious outbreaks.

For more, quality, information, stop watching the infomercials known as the nightly news, and check out real sources such as the CDC. Take prudent precautions, the same as you would take during any high-disease season. Wash your hands frequently, especially when you have been in public spaces, and see your doctor if you develop flu-like symptoms. But lets stop the panic and sensationalism, and instead use our brains to think.

Suing Your Parents' Genes

2009-04-12T08:58:00.005-04:00

It is said that people go into psychology to understand themselves...well, one of my main reasons why I went into genetics was to prove that I was not related to my family. That, of course, didn't happen - the Adams family is a more functional collection of misfits than my assortment of relatives, but now I may have a second option. Maybe I can sue my parents for the genetic material that they gave me.

Does it sound like I just took a break from reality? Maybe...but in today's world anything may be possible. A recent case in New York State may have set the stage for me to actually proceed with my lawsuit.

In this case, a law team representing a young girl has successfully convinced a judge to hear a case against Idant Laboratories - a sperm bank. The team alleges that the sperm bank provided the girl with cells from a donor that contained an allele for fragile-x syndrome, a genetic cause of mental retardation.

This case basically establishes that gametes, and the genetic information that they contain, may be considered to be a commodity, and are suing the labs on the basis of a "breach of the express warranty of merchantability". While the details of this case are very interesting, namely how several different labs differed in their results in screening for fragile-X syndrome, and how the lab is alleged for not discovering that the donor displayed symptoms of fragile-X. But even more intriguing is the fact that sperm is now a commodity. That is right, sperm may be now covered by a warranty, just like a TV or iPod.

Which leads me back to my parents. You may think that may approach to using the parents is just a get-rich scheme, but actually it may be the perfect solution for the high-cost of medical treatment. Luckily for me, as least so far, my parents did not give me anything by a colorful childhood and a decent dose of lunacy. I have suffered from anxiety-related issues my entire life, and given the pattern of inheritance in the male members of my family, I am sure that I can trace this trait directly back down my paternal line. But lets just say that I had inherited some sort of more-damaging, and costly genetic defect - maybe even fragile-X syndrome. Then, based on what this case may be proposing - I could sue my parents, and more important their insurance companies, for providing a defective product. In theory, if I could get DNA samples, I could go back multiple generations (we have plenty of loonies in our closet), and possible recoup the cost of my medical treatments. My children could then sue me, etc., etc.

In other words, while I do support the efforts of the family of this young lady to provide for their daughter and prevent future people from suffering from neglect - the courts need to be very careful with what precedent that they set on this one. One wrong turn and the insurance agencies will insist that everyone undergo genetic screening - and that their insurance rates be based on the results of that screening. I am fairly sure, especially if you have a family like mine, that you don't want people peeing into that closet!

Advances in Cancer.... Linking the Pieces

2009-03-20T10:00:00.004-04:00

As part of the Darwin Bicentennial Lecture Series at Appalachian State University, Dr. Paul Ewald, author of Plague Time: The New Germ Theory of Disease, recently gave a presentation on the genetic basis of cancer. During the lecture, Dr Ewald spent a considerable amount of time discussing the role of infectious agents, specifically viruses, as the causative agents of cancer. Specifically, Dr Ewald talked about the human papillomavirus (HPV), and how screening of seemingly unrelated cancers, such as breast cancer and cancers of the head and neck, are linking this virus as a potentially more important agent in cancer formation than previously thought.

If infectious agents are responsible for priming cells to enter into a tumor-forming stage, as Dr Ewald's work strongly suggests, then the use of vaccines against these agents could be a major advance in the evolution of preventative strategies against cancer. HPV vaccines are already recommended for young women to prevent against cervical cancer later in life. Now it appears that these vaccines may have potential benefits in other areas as well.

Interestingly, a recent article in Science Daily (Genetic Markers for Aggressive Head and Neck Cancers) presents data from a study at the Albert Einstein College of Medicine that a specific type of genetic markers, called microRNAs, may be used to identify individuals who are highly susceptible to forms of head and neck cancer. The researchers in this study propose that genetic screening may be useful in the development of new treatments for these cancers.

Is is possible that the microRNA markers identified by the team at the Albert Einstein College of Medicine are actually indicating susceptibility to the HPV virus? We know that everyone who carries HPV does not necessarily develop cancer, but the reason why is not yet clear. It could be that a genetic susceptibility is the key. Certain genetic combinations could promote HPV influence, and result in the formation of the cancer phenotype. If this is the case, then trials of using the HPV vaccine on individuals who have these specific microRNA markers are definitely in order. This could provide some very useful insights on new treatments of specific types of cancers, specifically those that have been identified to be associated with an infectious agent.

RicochetScience Goes Twittering

2009-03-15T15:19:00.003-04:00

The sign of a true geek is their desire to try out new tech - after all, new e-toys are like crack to a geek... and I am no exception. Although I have been a little slow in seeing the benefits of Twitter, I am beginning to come around. At first I thought that it might just be the next generation of social text messages, but now I am starting to see it in a new light - a new form of scientific communication.

Although I will always be a geneticist at heart, my research interests now focus on how to effectively communicate information quickly to students and interest groups. Obviously blogs are a component of that communication, but I also am experimenting with eBooks, Kindle, Nings, and Wiggios (these are for textbook development mostly). RicochetScience is already on Facebook.... and I am sure that there is more to come.

So if you have an interest in following some of the latest developments in science, with a strong focus on genetics, then go ahead and subscribe to my twitter post, RicochetScience. At least once a week I will send out posts about some of the more interesting stories in the news, and maybe a few links back to this site as well. Please feel free to email me at any time about your comments, good or bad - feedback is important!

And I promise you... you won't have to read any posts about what I am doing right now...

Jumping Genes and Stem Cells

2009-03-10T09:49:00.007-04:00

I have always held a fascination for transposons, or jumping genes as they are sometimes called. Part of this interest may be due to my background in Drosophila genetics, where a transposon called a P element has been used extensively for genetic manipulation of flies for years. But also there is the fact that P elements appears to have made the jump into Drosophila melanogaster only recently (with in the past 50 years). From an evolutionary perspective this is fascinating as it allows us to study how a genome (in this case Drosophila) responds to the introduction of a new transposon.

However, On another front, the study of transposons joined forces with the study of stem cells this week. Even though President Obama has reversed the ban on using embryonic stem (ES) cells in research, scientists are still actively pursuing methods of generation stem cell lines. of particular interest are the induced pluripotent stem cells (iPS cells - see "This Isn't Science Fiction Anymore"). iPS cells are adult stem cells that have been convinced to revert back to a more generalized (less specialized) state. Although iPS cells have only been around for a few years, they have created a definite interest in the scientific community. If a method of making iPS cells was simplified - then it may be possible to make stem cells out of almost any human cell type. This would practically eliminate the need for embryonic (ES) stem cells and open up new avenues for genetic research.

One of the main problems with the generation of iPS lines has been the genetic vector used to alter the cells. For the past few years this has focused almost exclusively on the use of viruses. The main problem with viruses has been the fact that they are very disruptive to genomes. When a virus integrates itself into the genome it has the potential to disrupt important genes or their regulatory regions. But there is now another way and it involves the use of transposons. Once of the benefits of the transposon is that it carries a gene called transposase, which is what promotes the movement of the transposon in the genome. It also means that the location of the transposon is transient - it can move in and then move back out again. Like viruses, transposons can be genetically engineered to contain other genes, in this case the genes to make a cell pluripotent. One of the transposons that has been selected to do this is appropriately named piggyBac. piggyBac is a rather large transposon (around 2,400 base pairs in length) that has been used in the past to perform genetic transformation in fruit flies and other insects.

What is now possible, at least in mouse trials, is to deliver a genetically engineered transposon containing genes for pluripotency into a cell. Then, once the genes have been expressed, and the cell has undergone a transformation into a stem cell, the transposon can be activated and the genes removed. Thus, if the transposon inadvertently inactivated a gene of importance, it may be removed from the gene with very little consequence. By doing this geneticists hope to greatly increase the potential of using iPS cells in research.

The Verdict on Autism

2009-02-25T13:38:00.007-05:00

Finally we can get down to some real issues regarding autism. As reported in this editorial in the Los Angeles Times, the US Court of Federal Claims has found no substantiated link between autism and the MMR vaccine or the vaccine additive thimerosal.

I have covered autism in two previous posts "The Question of Fragile X " (9/27/2008) and "Autism in the News " (4/4/2008). In both cases I have discussed some of the genetics behind this disease. For example Scientists know that autism is a multifactorial trait - meaning that it probably has both a genetic and environmental component. It is also most likely that autism is a disease that displays genetic heterogenity - meaning that it is actually several different diseases that express themselves the same way. Cancer is a good example of a disease with genetic heterogeneity - just because you get cancer does not mean that it is from the same cause.

Should we have never investigated the MMR vaccine or thimerosol? - of course not. It is always important for scientists to follow-up any leads as to a cause of a complex disease such as autism. However, numerous studies have indicated that the link between these and autism is almost insignificant. So why is this an issue? For too long the research community has been having to focus on only one cause - vaccines and their additives. This focus on one factor is not resource-friendly and it distracts from the search for a real cure. The results are in - time to move on.

There will be those individuals who accuse the government, CDC, and pharmaceuticals of a massive cover-up. Others will decide not to vaccinate their kids based on religious preferences. Neither of these two groups should be treated seriously since 1) our government is not smart enough to cover-up the simplest lie, and 2) the consequences of not being vaccinated far, far outweigh the risks.

We need to support autism research, even when the results do not match what we want. That is what science is all about.

Want more information - check out the National Institutes for Health pages on autism and the National Autistic Society page on autism genetics.

Neandertals in Our Midst

2009-02-21T18:26:00.005-05:00

The commercials featuring the Geico caveman made it seem as if a Neandertal could readily interact within a Homo sapiens society.... we may soon find out if that is true.

Recently, scientists at the Max Plank Institute of Evolutionary Anthropology in Leipzig Germany announced that they had completed the sequencing of the Neandertal genome.

Neandertals went extinct around 30,000 years ago - most likely because of an untimely interaction with the Cro-Magnon, our early ancestors. As was the case with most species on the planet, Neandertals did not fare well from their encounters with us. For some time scientists have believed that it may have been possible that Neandertals simply bred into the Cro-Magnon population and the two became genetically integrated. Based on the work of these German scientists, it is now clear that this did not happen. There is no significant evidence of a transfer of Neandertal genes into our species.

While nature intends for extinction to be permanent, our mastering of the molecular world has made it possible to bring some species back to life. Wolly mammoths, the dodo bird, and passenger pidgeons have all been nominated as species to be returned to the surface of the planet. We can now add a new species - the Neandertals.

Once the genomic analysis is complete, it may be possible to transplant Neandertal DNA into a chimpanzee, or even human, ovum. Since there is very little genetic difference between these three, there should be relatively few developmental probems. In fact, it is estimated that this could occur within the next few years at the nominal cost of around $30 million.

So what would we do with these Neandertals? We should decide that before we begin. Our initial instinct may be to put them in a zoo. But we should be careful about that decision. For although we may consider ourselves to be the evolutionary favorite - we may have just gotten lucky the first time. We now know that Neandertals possessed the gene for speech, FOXP2, and they had a larger brain size than ours, and had the at least the beginnings of culture. They may give us a serious run for our money this time around. Who knows, maybe this time they will let us integrate into their culture..... or maybe not.

Walmart Offers Genome Sequencing? Not Yet...But Maybe Soon

2009-02-11T10:20:00.008-05:00

Within the next few years it may be possible to go to Walmart, pick up a gallon of milk, and then stop by and have your genome sequenced while you wait. Sound unbelievable? Recent developments in the sequencing of your genome may make this a reality in the near future.

A company called Complete Genomics has recently announced that they intend to market the $5000 complete genome sequencing package. $5000 is not cheap, but it is definitely cheaper than some of the earlier efforts at genome sequencing.

The Human Genome Project cost 2.7 billion dollars, or roughly $1 per nucleotide in our genome. If the claims by Complete Genomics are correct, then the cost of having your 3 billion (+) nucleotides in your genome sequenced is be reduced to around $0.000016 each. And that opens the door for some pretty interesting developments....

First of all is the fact that the $5000 genome will ignite a form of biotech price war. When the first wide-screen plasma TVs hit the market, their average price was well over $5000. Many people wondered who would pay that much for a TV? But, very quickly, the price came down to the point where now you can get a wide-screen plasma for around $500. The same thing should happen with genome sequencing. Competition and technological advances will drive down the price, maybe even to less than $500. There is already financial incentive, the Archon X Prize in Genomics is offering $10 million to the first company to sequence 100 human genomes in less than 10 days. This is still a formidable task, but so was getting around the world in less than 80 days to Jules Verne.

The availability of inexpensive and rapid sequencing of individual genomes will be a huge asset to companies who need large databases for genomics work. Once these large databases become available, extensive association studies of the human genome become possible. These studies have the potential to reveal rare gene combinations that may be associated with some forms of diseases. This, in turn, has the potential to facilitate the development of new treatment options. As in any scientific experiment, the larger the database, the greater the chance of finding something rare and interesting. Right now, we are limited the availability of these large databases by cost...but it looks as if that may be changing.

Of course, there are real ethical questions that need to be addressed, mainly to do with the confidentiality of the genetics information and who ultimately owns the rights to your DNA. After all, the insurance companies would love to know about that rare allele you are hiding that will not only shorten your life (and time paying premiums) and cost them thousands in medical costs. We should be cautious of who has access to this information, but not so overly cautious as to delay development time of new technologies. In the long run, the availability of inexpensive genomic sequencing will advance medicine in ways that are currently only science fiction.

For more information on the work being done by Complete Genomics, see the article by Peter Aldhous "Genome Sequencing Falls to $5000"

Genetics Community Online

2009-01-21T16:45:00.004-05:00

Nature Publishing Group has just released a new genetics education website called Scitable. It represents a new generation of making science content and experts available to undergraduate students and the general public. My first impression of this is that it is pretty impressive. Community-based learning is widely recognized as an effective learning strategy, and it will be interesting to see how scientists, students, and the general public react to Scitable.

For more on the potential uses of Scitable for developing a genetics community - see my column on ScientificBlogging.com. For now, check out the site and let me know what you think. Should this be the way that education is addressed in the future?

Links for Scitable were repaired on January 23rd

This Isn't Science Fiction Anymore

2009-01-16T18:42:00.003-05:00

Sometime an event occurs which makes it actually look like I might know what I am talking about.....

This past week in my human genetics class, we discussed the possibility of turning back the clock on adult stem cells to make them behave like embryonic stem cells. The lure of embryonic (or ES cells) is that they have not yet realized their genetic destiny, and therefore have the potential to become any stem cell. Of course, the main problem has been where ES cells were obtained from - most cells come from left-over in vitro fertilization (IVF) events, and some people have expressed a concern over the ethical use of these cells.

In the December 10th edition of Science (vol 322, issue 5099), the editors of the journal awarded the 2008 Breakthrough of the Year to the process that generates an induced pluripotent stem cell, or iPS. iPS cells are adult stem cells that have been genetically altered to behave like ES cells - opening up the possibility that they may be developed as a alternative source of stem cells. Furthermore, research in this area has suggested that it may be possible to develop iPS cells as a form of treatment for a wide variety of diseases, including Down Syndrome, Huntington disease, and juvenile diabetes. Anyone who has an interest in stem cells, and the future of medicine, should definitely read this article. Sometimes the facts are more interesting than the fiction!

Synthetic Biology 2.0

2009-01-15T20:25:00.000-05:00

While the scientific community, and most of the intelligent world, has widely accepted that the theory of natural selection is underlying mechanism of organic evolution, until recently our studies of evolutionary processes have been confined to the examples from a small plant orbiting an insignificant star in a mid-sized galaxy. From this limited viewpoint we know that evolution is intimately connected with life... but as scientists, we would love to expand the reaches of our database.

The study of synthetic biology was until recently a theoretical science. Engineers, biochemists, and geneticists proposed mechanisms by which molecules and cells could evolve the basic characteristics of life through pathways other than those found on Earth. However, in recent the study of synthetic biology has progressed from a theoretical to an applied science. For example, we already know that it is possible to change the structure of the genetic code in the laboratory (see "Synthetic Life Makes Synthetic Proteins"). Now, researchers at the Scripps Research Institute have demonstrated that RNA molecules can evolve the ability to increase replication efficiency in the lab (see "Artificial Molecules Evolve in the Lab"). Each of these steps brings us one step closer to truly understanding life.

There is little doubt that the work of the researchers at the Scripps Research Institute demonstrates an evolutionary process. However, some will still argue that this is just another lab-based example of evolution, and that we don't really know for sure that the system demonstrated in the lab would work in the "natural" environment. The true test of whether synthetic biology is a viable demonstration of natural selection will only come when we finally get a glimpse of proto-life on other planets and moons. Europa, Titan, maybe even Mars, may hold "snapshots" of how early chemical evolution occurred. For too long biologists have focused simply on life on this planet. If we truly want to understand evolution and life, we need to start expanding our horizons.

Book Review: What is Life?

2008-11-23T17:04:00.005-05:00

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.

The Death of Junk DNA and Birth of the Junkome

2008-11-18T17:17:00.001-05:00

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

Dr Google

2008-11-12T15:01:00.004-05:00

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.

The Return of the Sloth?

2008-11-09T17:10:00.007-05:00

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

The Battle Against Viruses Heats Up

2008-10-27T15:44:00.003-04:00

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

Fruit Flies Enter the Political Battle

2008-10-25T22:10:00.002-04:00

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 24^th 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

2008 Nobel Prize in Chemistry

2008-10-09T16:48:00.007-04:00

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.