Oh Baby: The next step in DNA sequencing

Somewhat ironically, as a geneticist, my favorite Sci-Fi movie of all time is Gattaca.  For those that have not seen the movie, it's a story set in the future where most babies are born with the help of genetic  preimplantation diagnosis so as to select out undesirable traits.  Children conceived the traditional way are discriminated against because they are thought of as inferior.  Moments after children are born, a genetic profile is run on them and predisposition to any illness and disease is determined.  This information is then used against these children in all aspects of life.

We've discussed several times on our blog about the many ways that personalized medicine and DNA sequencing is the wave of the future.  I believe it will even become the standard of care.  The question remains, however, just when does a person get their DNA sequenced?  Screening babies at birth could potentially provide the most useful information as their genetics could be used to make medical decisions prior to any illness manifesting or any medication having an adverse reaction.  There is, however, a fine line between the dystopia of the world presented in Gattaca and the usefulness of genetic information in aiding modern day medicine.  A new project called BabySeq aims to determine just this.  This study was recently funded and will examine the risks and benefits of comprehensive genome sequencing in newborns from both a physician and parent standpoint.  Although a relatively small study and only the tip of the iceberg, it should be an interesting nonetheless to see the results.

Personalized Medicine is a Two Way Street

I recently had a “conversation” with someone I know about a medication he was taking for a sinus infection.  I put conversation in quotes because this person, a fairly well educated individual, had no idea what medication he was prescribed and was taking it blindly.  I know I am the opposite end of the spectrum and am the girl that reads every word of the medication package insert, but still.  To not even know the name of the medication you are taking is, dare I say, irresponsible.  And yet we wonder why physicians prescribe medications that interact with others causing potentially harmful adverse drug-drug interactions when there are individuals walking around that have no idea what pills they are popping.  How could a doctor know medication A might interact with medication B if the patient can’t even tell you they are taking medication B?

I hear this a lot from people I meet—“The doctor knows best so I’m just going to take what she gives me or do what she says”.  Yes, our medical professionals are the experts, but no one is exempt from making mistakes.  And who better to take charge of our own health than ourselves?  It is naïve to think that the future of health care should be left in the hands of people that see us just a few times a year, if that.  As the medicine paradigm shifts towards being more personalized, we the consumer need to recognize that this is a two way street.  As health care providers tailor tests, medications, and treatments to our own individual unique genetic makeups, we as the patient need to also tailor our own view on healthcare and take steps to personalize our experiences as well.  This is different than Google-ing symptoms and making self-diagnostic predictions about what disease you might have.  But it does mean being responsible for your own health and wellness and knowing your body.  Know why your physician is prescribing you a medication and what it is treating.  Know why your doctor is ordering a test and what it will tell her.  Keep records of your health history and make note of anything out of the ordinary.  This information can be not only useful to yourself, but also to any health care providers you may see in the future and can help them personalize your care.  Being responsible for your own well being is the best step you can take towards living a healthier life. 

The Human Genome Project

One of my many “hats” at my university is to teach 1^st year veterinary students about the wonderful world of genetics. The great thing about 1^st year students (or college students in general) is that they tend to get bored. So this year, I was really doing my research, trying to find interesting and fun facts about genomics to hold and keep their attention. I stumbled on some research about the human genome project that I thought ya’ll might be interested in.

In order to determine “mutated” genes or gene alleles that cause cancer or disease or whatever aliments you’re interested in, one needs to know what the “correct” gene looks like. In order to do that properly, every single gene, which is greater than 40,000, of the human genome must be identified (also termed sequenced). The genetic code is a bunch of As, Ts, Cs, and Gs (termed bases), 3.3 billion of them to be exact. So the process of determining and reading 3.3 billion ATCG’s was not only a long process, but also a costly one. The project took 13 years for a team of scientists to complete and cost $3 billion dollars, so about $1 and 0.1 seconds per base. With such a large investment of time and money, it got me thinking about how the information was collected and how useful it was…

In order to read the bases, you need to have someone’s DNA. So, who was the lucky guy or gal that donated their genome for this massive project? I’m not going to get into the ethics of this, but did find out that scientists wanted to keep the identity of the DNA donor anonymous so they got 40 people to donate blood (half males and half females), and randomly selected 2 females and 2 males to use. However, the DNA quality of the 4 samples was very different and the majority of the genome sequence was from a single donor, only to be identified as RP11. Therefore, this “RP11” person’s genes are now known as the “normal” genes used to compare everyone else’s genes to. What is to say this RP11 is “normal” and his/her genes are the “correct” ones?

I think our society has progressed significantly in the last 20 years, but many questions still remain unanswered. There is just so much genetic information in a single person, that we can’t possibly know all the answers. If it took 13 years to read the genome of a single person, think about how long it would take for everyone to get their DNA read. As a scientist, studies like these are very interesting and I hope I was able to hold your interest too. Just a little fun food for thought for a Thursday afternoon!

Is DTC good for the Consumer? Part 2: LDTs

In the wake of the Myraid Genetics ruling, the doors opened for more companies to commercialize genetic tests and it finally happened--crowd funding of a genetic testing company.  Specifically a Direct to Consumer (DTC) genetic testing company.  See this article and this website.  For a mere $99 you can have your genotyping run to determine which medications may work best for your genetic metabolism issues.  But can you trust the results?

One of my first blog posts was about direct to consumer testing and the perils it poses when this information is used without a clinician's oversight.  That is just part of my issue with DTC testing. So far, the FDA has been rather wishy washy about regulating "lab developed tests," known as LDTs, for genetic testing.  This means that every lab can develop their own genetic test protocol--no standardization and no FDA oversight.

Now there is the College of American Pathologists (CAP) and Clinical Laboratory Improvements Amendments (CLIA) and they are supposed to be the governing bodies for LDTs, but why not make each test get FDA approval?  Especially if, as Genome Liberty advocates, we should be acting upon the information gained from a DTC LDT.  Would you want the device that gives you a blood sugar reading to be based on a LDT with no standardization or oversight?

Some will argue this will limit competition as FDA approval is expensive--so many of these pop up DTC labs would disappear and the cost of genetic testing will rise. Good, they should.  In my opinion, LDTs should be regulated by the FDA and should rise to the level of scrutiny you would expect from a lab test where clinicians rely on the results to make patient decisions.  Where consumers rely on the results to make lifestyle changes.

On June 5, 2013, the FDA Commissioner Margaret Hamburg probably said it best: Hamburg warned that "advanced diagnostics to make critical, potentially life-altering treatment decisions exposes patients to obvious risks if these tests do not perform as expected," and "false results put patients at risk for a mis-diagnosis or a wrong diagnosis that could result in inappropriate treatment or no treatment at all."

1.  BRCA testing can identify high risk breast cancer patients, so when a woman makes the agonizing decision to remove her breasts because she has done BRCA testing, THAT TEST BETTER BE RIGHT!

2.  Genetic tests are available to determine metabolism of certain blood thinners, but if the dose is too low you could get a blood clot (stroke) and it can cause hemorrhages if the dose is too high, so when a doctor decides to alter your initial dose of a blood thinner because your genetic test says your metabolism is different from normal, THAT TEST BETTER BE RIGHT!

3.  Codeine is metabolized into morphine and high doses of morphine can be lethal to a child, so when a child is given the normal dose of codeine for pain management because their genetic test says they are a normal metabolizer, THAT TEST BETTER BE RIGHT!!!

You have no way of knowing the level of experience and education of the person developing the LDT, the quality control standards used to verify test accuracy and repeatability or the overall reliability of LDTs.  I propose a higher level of standardization and oversight.  If a company stands behind its LDTs, they should have no problem getting FDA approval.

Instead of bemoaning that FDA approval slows down innovation, the FDA should come up with a way to categorize risk and streamline the approval process.  Faster innovation isn't always better innovation.  Quality over quantity.

Off soapbox now!
-Christina

The Genetic Athlete

Much attention has been paid to the recent decision by the American Medical Association to make obesity an official disease.  Although certainly lifestyle choices play a part in this, in some people genetics clearly play a role.  So what about the other extreme- do genes also play a role in athleticism?  The answer is similar - clearly it is a combination of lifestyle chocies and genes that make a great athlete.  As an avid CrossFitter for over 4 years now, I have come to accept that my athletic ability is limited no matter how hard I train.  Watch any sport at the professional level, however, and you will notice that often athletes, especially within the same sport, have similar body types and abilities.  Is this due to years of training and conditioning, or does DNA play a role?  In a new book  titled ‘The Sports Gene’ (which I caution I have not yet read but is on my list of to-read), author David Epstein explores this very question.  It may not be a surprise that the answer is yes, but it appears the things we may assume are genetic are not, and vice versa. 

Given DNA clearly does play some role in determining who becomes a great vs. mediocre athlete, however, the bigger question is will this translate into personalized medicine in the future?  I can imagine a situation in which knowing this genetic information might help doctors treat injuries or help those of us not as endowed with athletic genes to overcome some of our biological barriers.  Perhaps knowing this information will also help those with musculoskeletal disorders function easier.  Further still, will genetic information be used in the future to screen athletes as part of tryouts?  It is an interesting question that remains to be seen.

Using Genetics to make the Flu virus more deadly

The human genome is very complex, consisting of 23 pairs of chromosomes, that contain over 3 billion base pairs of DNA, that encode for over 20,000 genes. All 20,000 of these genes have a function, and allow us to perform our daily tasks. Just like humans, viruses also contain a genome, containing DNA that allows it to infect plants or animals, proliferate exponentially, and infect other cells. Unlike humans, viral genomes are small and simple since they infect host cells and use their host to carry out most daily functions.

A few years ago there was a deadly outbreak of the H5N1 subtype of the flu virus. The media referred to this highly-contagious and deadly strain of flu as the "bird flu" since it was only able to transmit from bird to bird. Even though this strain of flu could only infect birds, it was very deadly and caused a panic in people who feared that the virus could mutate rapidly into a highly-contagious and deadly HUMAN virus.

The H5N1 flu virus has 13,500 base pairs of genetic information, that encode for only 11 genes. So you can see, viruses are much less complex then humans. In fact, the genome is so small that scientists in labs can re-create the genome and use genetic tools to introduce mutations to change the gene functions of the 11 viral proteins.

Last year, a group of scientists who feared that this "bird flu" could easily cause a pandemic outbreak in humans, began to study the 11 H5N1 genes. They used genetic tools to introduce single base pair changes in the H5N1 genome. They found that by creating as little as 5 mutations in the virus they could create a virus that was capable of infecting mammals. Therefore, these scientists have used genetics to create a virus capable of causing a world-wide pandemic flu outbreak. 

If you want find out all the details to make your own deadly virus, the article can be found here:

Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets 

Yes, these scientists have good intentions and won't release it into the population. However, these types of studies illustrate the power of genetic mutation and feasibility to create deadly pathogens/toxins to be used in terrorist or warfare attacks.

Finally, here is a little video from Hank with his interpretation of  the mutant flu. Enjoy!

Medicine's Holy Grail

 

A few weeks ago, CBS Sunday Morning featured a segment about Alex's Lemonade Stand and advances in treatments for childhood cancer.  It is a truly moving human-interest piece that touches also on the Holy Grail of medical research.  The cure for cancer.  You may be wondering, “what’s the cure for cancer got to do with personalized medicine?”  This is where I tell you – it’s got EVERYTHING to do with it.

For all of the advances in medicine over the past century, one of the biggest mysteries is still cancer.  Medical science is only just beginning to understand and explain why cancer happens, and even then, it’s not the same for every person or every form of cancer.  Going back to the segment on CBS Sunday Morning, one of the things discussed is the discovery that certain types of cancer seem to be linked to a mutation in a gene called anaplastic lymphoma kinase (ALK).  More and more cancer diagnoses are starting to sound like alphabet soup: HER2 positive or negative breast cancer; BRAF mutation in melanoma; chronic myelogenous leukemia (CML) caused by BCR-ABL; colon cancer with or without K-ras mutation.  It can be confusing and it is definitely overwhelming, but here’s what you need to know:  THIS IS GREAT.  Why, you ask? 

Here’s why…One of the biggest shifts in recent years is how cancers are treated and managed.  Therapies and treatments have moved from a generalized “attack every fast growing cell” to a targeted approach.  Having this genetic level of specificity allows modern science to get at the root of what’s causing the cancer cells to grow and thrive.  For example, the ALK mutation that drives certain types of lymphoma seems to be turned off by the drug crizotinib.  In some cases, the treatment has been so successful, that the cancer is quite literally GONE.  Finis. Cured.  Those are some pretty amazing results.  We can get those results because the therapy is acting at the source in a highly specific manner.  Another positive outcome to therapies working at the source is that the side effects are far less than what you see with traditional chemotherapy.  Newer therapies have mild to moderate side effect profiles allowing patients to continue with daily life versus their older chemotherapy counterparts.  Sadly, those cases where cancer disappears completely are still the exception.  Many treatments still fail and cancer progresses.  Treatments that work amazingly well in some patients don’t work at all in others, and scientists don’t always know why.  More research and understanding will be necessary before that miracle cure is found…but there’s promise.

The drug development pipeline is rich with products that are highly specific to a disease type.  Therapies for diseases you’ve likely heard of: fibromyalgia, lupus, multiple sclerosis; and diseases you’ve probably never heard of: Fabry Disease, hereditary angioedema, alpha-1 antitrypsin deficiency.  One of the very exciting things about the drug development pipeline is that ~40% of it is cancer therapies.  Even more exciting is that many of these therapies are oral, not infused.  Unfortunately, the downside to these highly-specific therapies means that they treat only small numbers of patients comparatively.  It doesn’t sound so bad until I tell you that the price goes up when the number of patients treated goes down.  Many of these therapies are at or above $100,000 per year.

In subsequent posts we can dig into the specifics of some of these new therapies.  A lot of these new products entering the market come with companion testing that is required in order to qualify for treatment.  Personalized medicine is here to stay.  We’ll help you become educated.  Ask us your questions, tell us your thoughts.

-A