Some students I was teaching thought that this might be possible: to engineer the insulin-producing cells with a correctly functioning gene, a type of gene therapy.  While this has been a goal for researchers, and they have successfully made insulin-producing cells in the lab from embryonic stem cells, they are not appropriate for transplant because they do not release the insulin in response to glucose levels.  Plus, the immune system might still recognize these cells as foreign and destroy them.

So a new study is looking at transforming cells of the gut that don’t have a specific job yet.  These cells receive signals throughout the life of an individual to become many different types of cells that are used for normal gut function.  So could they engineer these cells to receive the signals to become insulin-producing cells?  Also, would the cells only release the insulin in response to blood glucose levels?

Two Columbia University researchers have started finding possible answers to these questions.  Once they turned off a gene that normally plays a key role in the fate of a cell, insulin-producing cells were generated.  Having cells in the gut that make insulin can be dangerous if they did not release insulin in response to blood glucose levels, but these “new” gut cells have glucose-sensing receptors to allow them to do just that. Another remarkable feature was that the gene could be turned off either early on in development, or later on in adulthood, so it wouldn’t matter how old the patient was.

The next step is to take the research that has been done on mice so far, and see if they can mimic this in humans with the use of a drug or chemical.  This method will also need to prove to be safe and more effective than current methods of treatment, not just to avoid the burden of daily injections.

While most students don’t fully grasp this idea, there are a few examples we can use that can help to explain this.  I have always used examples of giraffes and the development of long necks, or antibiotic resistance in bacteria, but these seem to be a bit out of the realm of many 5^th grade students.  So what better example than ourselves!

During another lesson, I introduced the development of lactase persistence, or having the ability to drink and eat dairy products past infancy.  Digesting the sugar in milk (lactose) is dependent on whether or not the cells of your small intestine are producing the enzyme lactase.  Lactase is responsible for breaking lactose into smaller components that then get absorbed into the bloodstream.  For mammals that get milk from mother early in life, this enzyme is essential.  Would a mutation in the DNA that would allow a cell to continue to make lactase past infancy be beneficial?  It all depends on which population of humans you ask.

If it is a population of humans that began drinking the milk of other animals after the development of agriculture, like those of Northern European descent, it would be selected for.  These populations now show the highest frequency of lactase persistence among all human populations.  If dairy was not a part of your diet after infancy, this mutation wouldn’t be considered beneficial and would not have been selected for, such as in African, Asian and South American populations.

So, when teaching evolution and the changes that we see in species over time, it is nice to be able to give an example that we can see in humans.  Using an example that is a recent development in humans over the last 10,000 years, may help students to understand this concept better, and apply it across any species.

This has recently been reported for patients with Hemophilia B.  Hemophilia B, also known as Christmas disease, is due to a deficiency of the clotting factor IX (FIX).  The first reported case of Hemophilia B due to a decrease in FIX was in 1952, and was called “Christmas Disease” after the first patient diagnosed was named Stephen Christmas.  Without this clotting factor, the blood does not form clots and results in severe bleeding episodes, especially in the joints and muscles.

Bettert reatment for this disorder began back in the 1960’s where they would inject FIX concentrates into the blood of patients with hemophilia B.  This increased the average age of death of 24 to a median lifespan of 63 years of age.  So with the success of the protein therapy, why try to fix the genes?  With each treatment costing $150,000 to $300,000, a patient needing clotting factors for hemophilia could incur a lifetime cost of $20 million.

So there needs to be a way that a patient can have a more effective treatment option that will cost less.  This new treatment option offers some hope.  Using a new virus for the administration of the gene, patients have seen an increased production of FIX protein for longer periods of time, and were able to stop or decrease the amount of concentrate injections they would need.  With one injection of the virus only costing about $30,000, dramatic cost savings have already been seen.  While this does offer new hope for the treatment of clotting disorders, follow-up with a larger number of patients and for longer periods of time will be needed to fully weigh the benefits and risks of this technique.  Once this has been done, hopefully we will see gene therapy used more in practice and maybe even for more than just clotting disorders.

Ponder, Katherine P.  Merry Christmas for Patients with Hemophilia B. The New England Journal of Medicine 10.1056; December 10, 2011.  Nathwani A.C., Tuddenham E.G.D., Rangarajan S., et al.

So we got into a discussion about model organisms, those that are used as a good system to be able to compare back to human beings, and in what ways they are being used.  That we have to even figure out whether or not something has a genetic basis.  Or maybe a good treatment option for a genetic disease.  If an organism shows similar symptoms as a human disease, this will give us a better understanding on when and how the disease progresses, causes and possible treatment options.

This allowed one student to immediately jump into what causes Autism.  We talked about the controversy that surrounds the disorder, and ways scientists are trying to figure out the genetic basis of the disease, and how much the environment can play a role.  In our current discussion, it was a perfect way for me to bring an actual example of how other organisms are being used to find out more about a specific disorder.

It was shown by a group of researchers at Cold Spring Harbor Laboratory that a deletion of a group of genes on chromosome number 16 causes autism-like symptoms.  They used mouse models with the same genetic alteration to show that when fewer copies of these genes are inherited, it leads to features resembling those that are used to diagnose autism.  Changes were seen in the structure of the mouse brain (see image below) and in their overall behavior of the mice.  Using the mouse model, they are able to mimic the disease to better understand what causes it, better diagnose it, and a new possible target for intervention and treatment.

Image from http://www.cshl.edu/Article-Mills/cshl-team-finds-evidence-for-the-genetic-basis-of-autism

Image from Nature Reviews Genetics 3, 941-955 (December 2002)

While this technology offers the hope to increase the success of IVF, it does raise some concerns about choosing a child in order to meet the needs and desires of parents. While most cases seem to have parents that are trying to increase their chances of having a viable pregnancy, some have raised some major ethical dilemmas. For example, two parents with achondroplasia, a disorder of bone growth that causes the most common form of dwarfism , is caused by having only one mutated copy of a gene. These parents might want to avoid an embryo that receives a mutated copy from both parents, which would be lethal. Instead, would they possibly choose an embryo that only has one affected copy, which would result in a child with achondroplasia, instead of an unaffected embryo? Would an unaffected child suffer more in an achondroplastic family than an affected child in such an environment?

This technique can be applied in a variety of ways, but I wonder if there are more ethical concerns than anything else. With any new technology, just because we can, should we? Are parents going to do this just to have a child free of genetic disease? Or is the future of “designer babies” closer than we think?

Of course, everyone asks me what I think about National DNA Day, to which I usually reply, “Every day is DNA Day at the DNA Learning Center.”

DNA is business as usual for me and legions of genetic researchers and counselors, but its also becoming business as usual for a lot of average people who are interested in their health or genealogy.

People also often ask me how I feel about all the personal DNA data that is becoming available. To which I usually reply, “I’d be a lot more concerned about losing a credit card or my social security number than having someone look at my DNA.”

An amazing amount of personal DNA information is becoming affordable to the interested person willing to provide a saliva sample by mail. With the tag line “genetics just got personal,” the company called 23 and Me will provide a sophisticated scan of DNA extracted from saliva for less than $500. The company uses research-grade methods to scan more than 600,000 DNA variations to provide risk information about 150 diseases and health-related traits – as well as genetic ancestry. Several other companies will do a similar analysis at a competitive price. So far, only several tens of thousands of people have actually taken these companies up on their offer of a (relatively) cheap gene scan, messing up their business plans.

It may be that people are holding out to get the whole ball of wax. DNA sequencing is becoming so inexpensive – forget the gene scan – it is becoming trivial to determine a person’s entire DNA code, or genome. To date, whole genome sequences have been published for only about 20 humans, but the 1,000 Genomes Project will increase that number 50-fold. We are only a year or two away from the day when an entire human genome sequence can be generated a cost of $1,000 – the price of a middling refrigerator.

Ethicists, who tend to be people who worry a lot, have done a lot of worrying about the consequences of such genetic knowledge. On a personal level, will a gene scan take on the aspect of genetic tarot, predicting the future course of our lives? What will it be like when we have a precise catalog of all the good, bad, and middling genes—and the wherewithal to determine who has which? In the face of such knowledge, will society continue to acquiesce to those who prefer to let nature take its course or will we gravitate toward a prescribed definition of the “right” genetic stuff? Heavy stuff for sure if you or your family is facing a life-threatening disease or if you think hard about the sort of genetically stratified world envisioned in Brave New World, GATTACA, or The Island.

These scenarios aside, the truth is that, for most people, all this DNA data may be more banal than anyone could ever have imagined. (What, no ethical dilemma?) The original human genome sequence was a composite from several anonymous individuals, for which an extensive informed consent protocol had been followed. However, on becoming the first known individual to have his entire genome sequenced, Nobel Laureate James D. Watson promptly released it all online – with the exception of the ApoE gene that estimates his risk of Alzheimer’s disease. Watson’s sequence has been available for public examination since 2007, with no ill effect to him.

About 400 letters of my genetic code has been in an anonymous online database for several years now, and it hasn’t caused me any grief either. We have the same DNA sequences from about 50,000 students stored in the same anonymous database, and they haven’t caused any alarm. At least I haven’t gotten a single phone call from an irate parent in the 10 years since we started putting the sequences online.

That doesn’t mean we should be cavalier about what we do with our personal health information, including certain DNA data. But I think we’re pretty well covered by the Genetic Nondiscrimination Act of 2008, which prohibits insurance companies or employers from using personal genetic information against us. Besides, there’s just so much DNA data becoming available, no one has time to look at it all – any more than anyone has enough time to keep up with their emails. There’s just too much stuff in cyberspace.

So, I’m not being flippant when I say that I’m not very worried about the proliferation of DNA data. It’s only that there are plenty of other types of data that are more readily available and can hurt us more directly.

That’s why I always carry my wallet in my front pocket.

In contrast, there was a an effort to prevent hereditary blindness within the eugenics movement. Its proponents collected pedigrees, drafted legislation to prevent marriage of blind individuals, and surveyed ophthalmologists to assess causes of blindness and the cost to society to provide for the blind in specialized homes and schools. Their intent was to eliminate blindness in future generations. However, this was eugenics because affected individuals would not have been allowed to decide for themselves if the trait was undesirable, or what steps to take eliminate it.

Pedigree of a family with blindness

Explore the Eugenics Archive, especially the “Hereditary Disorders” topic, for many examples of how eugenicists viewed inherited diseases.