Chinese Herbal Medicine

When I tell people I used to research about the genetics of myopia (or nearsightedness),  one of the questions they ask is whether they’ll pass it to their children.

And I tell them there are other factors, “interactions” we call them, between our genes and our environment that determine if certain genes will express and/or be passed to our children.

For example, mutations in the brca1 gene are highly associated with very high risks of breast cancer. A brca1 (breast cancer 1; on chromosome 7) is one of the genes in the body that suppresses tumors, by repairing damaged DNA. A mutation or defect in the gene produces a protein that can not repair DNA in other genes. A person with brca1 mutations has up to 80% risk of having breast cancer in one’s lifetime.

However, not everyone who has breast cancer has the brca1 mutation. So, there must be other causes or factors that brought about cancer, which may have nothing to do with brca1. Some of the environmental risk factors for developing breast cancer include recent use of birth control pills;  earlier start to the menstrual period; postmenstrual hormone therapy, alcohol and many others (see list here).

Disorders that may be affected by genes and environment (risk factors) include other cancers, autism and other behavioral conditions, eye diseases like myopia, asthma and allergies, heart diseases, obesity… the list goes on.  Genetics parlance refers to these as “complex disorders“.

In contrast, there are medical conditions that are 100% genetic, referred to as “Mendelian disoders“.  Having a defective gene means the person is affected by the disease, and passes the gene to his/her children. These disorders can be diagnosed before birth, usually through a genetic screening test at pregnancy. Examples include downs syndrome, cystic fibrosis, thalassemia, phenylketonuria,  sickle cell anemia, hemophilia A, Tay Sachs’ disease.

What I’d like to do this month is look at some of the complex disorders and the environment and genetic risk factors involved. We’ll start with myopia or nearsightedness, but let me know if there is a disease you’d like me to focus on as well.

Has your mom ever told you not to watch TV too closely? Have you been told as a child that reading too much (or cross-stitching too much) will hurt your eyes? That’s not too far out an idea, at all.

Myopia or nearsightedness is a condition where one has trouble seeing objects that are farther away. Symptoms, usually developing in early childhood and teen years include squinting when trying to concentrate on an object far away, or holding an object very close to the face (to read, or to see it clearer). The person may want to sit very near the TV or computer close, and prefer to sit in the front of the class.

But does this mean that close-work and intensive reading cause eye problems?

Studies have shown that myopia is more common in some populations, such as the Ashkenazi Jews and Taiwanese where intensive studying and reading are encouraged; and in Singapore where certain jobs are visually-demanding. So certain kinds of exposures and tasks may contribute to myopia. BUT this is only part of the story.

Genes also play a major part, and plenty of studies already show that myopia is passed from parents to children. For example, myopia is more common in children of myopic parents than children of non-myopic parents.

So if scientists can identify myopia genes, treatments can specifically be created for children who are genetically more likely to develop myopia. Perhaps drug or gene therapies can even help make the condition less severe.

Tomorrow, we’ll look at some of the promising findings that point to genetic  factors of myopia.

image: Flickr

Competition is certainly good for us. One by one, the big league universities in the Boston neighborhood are going OPEN ACCESS.

Open access publishing means that research works can be read (online) and used freely by the public without paying subscription fees to journals and publishers. I know personally how expensive it is to subscribe to just one journal, and the information from abstracts are really so limited that having more open access journals is just good for the science.

Last January, the University of California and publication giant Springer agreed to have articles written by UP-affiliated authors to be published immediately and in full, even if the rest of Springer’s articles remain subscription-only.

In early February, Harvard University’s Arts and Sciences agreed to support an open access system. Harvard faculty will also be required to only submit to journals that will publish their work online immediately after acceptance for publication. Following suit, Boston U and MIT independently announced that the work of faculties all across their universities will be accessible to the public for free.

Lest anyone get the wrong idea: Open access is not free. University libraries have to pay open-access journals to have their research published, and the cost for pre-pay memberships have gone up in the last few years. The public does not need to pay subscription fees, but the researchers do. So, MIT will now be storing their research materials at the MIT DSpace : http://dspace.mit.edu/. Boston and Harvard are also working on their own online repositories.

Hopefully, more universities will follow and set up their own websites, or partner with publishers to get the cost of publication lowered and open-access more available.

Image: sxc.hu

Asians would know what I’m talking about. You drink a few sips of alcohol and suddenly, you feel nauseated and hot, you face turns beet red, and your heart beats faster. Known as the “Asian Glow” or “Asian Flush”, this reaction to alcohol is a risk factor for cancer of the esophagus, one of the deadliest in the world.

The alcohol flushing response is an inherited genetic trait – deficiency in the enzyme aldehyde dehydrogenase 2 (ALDH2)- common among one third of Japanese, Chinese and Koreans.

Here’s how the enzyme works: In normal individuals, alcohol is broken down into a non-toxic forms by the action of two enzymes.

1. Alcohol dehydrogenase (ADH) oxidizes alcohol into acetaldehyde. Acetaldehyde is a carcinogen that causes DNA damage, so the final steps in the metabolism of alcohol help get rid of this mutagen.
2. Aldehyde dehydrogenase 2 (ALDH2) oxidizes acetaldehyde into acetic acid and CO2.

When ALDH2 is deficient, acetaldehyde accumulates in the body and creates an unpleasant flushing reaction. A person homozygote for the inactive ALDH2 gene has a completely defective enzyme and can not tolerate even small amounts of alcohol, essentially protecting them from the acetaldehyde carcinogen. However, a person heterozygote for the ALDH2 gene would only have decreased enzyme activity, which means they may grow to tolerate the unpleasant reaction to alcohol and become habitual heavy drinkers. It is this group of alcohol consumers that is associated with the greatest risk in esophageal cancer.

A collaboration between Japanese and American scientists found that 8% of the world population (540 million) have ALDH2-deficiency and exhibit the telling flushing response when consuming alcohol. Physicians can counsel ALDH2-deficient patients to lessen alcohol drinking and decrease the risk of esophageal cancer.

Read more about the study in the PLOS Medicine issued on March 24, 2009 - The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption.

Image: PLoS Med 6(3): e1000050 doi:10.1371/journal.pmed.1000050 (CCAL)

Presently available medical technology is always crude when compared with what's presently taking shape in the laboratory. Take cancer therapies, for example: unpleasant and painful chemotherapy remains the state of the art in the field, but laboratories are turning out targeted therapies with next to no side-effects, or using the immune system to eliminate cancer.

This vast gap between lab and clinic is made particularly pronounced by the heavy burden of regulation that ensures commercial development of new therapies is expensive and slow, where it takes place at all. Yet even with this ball and chain, and even lacking the impressive technology still in trials, trends in results of therapy are still moving in the right direction. This is aptly illustrated by this data on cancer survival:

New data and analyses from a long-running study of cancer survival in Europe have shown that the number of people actually cured of cancer - rather than just surviving for at least five years after diagnosis - is rising steadily.

A special issue of the European Journal of Cancer [1] containing reports from the EUROCARE-4 Working Group, includes, for the first time, an estimate of the proportions of patients who are cured of their cancer in Europe and who, therefore, have a life expectancy equal to that of the rest of the population. The analysis divides patients into two groups - the proportion who may be considered cured of their disease and who are likely to die of something else, and those who will die of their cancer.

The study compared two periods - 1988-1990 and 1997-1999 - and found the proportion of patients estimated to be cured of lung, stomach and colorectal cancers increased from 6% to 8%, from 15% to 18% and from 42% to 49%, respectively.

...

"Geographic variation in the estimated proportion of patients diagnosed in 1988-1999 who were cured ranged from about 4% to 10% for lung cancer, from 9% to 27% for stomach cancer, from 25% to 49% for colon and rectum cancer, and from 55% to 73% for breast cancer."

There's a long way to go in terms of defeating cancer if you just project out that trend - but the work presently taking place in the laboratory goes far beyond trend continuation. The next generation of cancer therapies are completely new approaches and technologies that can be expected to greatly increase survival rates where they are deployed. This makes it all the more frustrating that we are saddled with a regulatory prison that prevents and discourages new medicine.

Regulatory bodies like the FDA have every incentive to stop the release of new medicine: the government employees involved suffer far more from bad press for an approved medical technology than they do from the largely unexamined consequences of heavy regulation. These consequences go far beyond the obvious and announced disapproval of specific medical technologies: the far greater cost lies in all the research, innovation and development that was never undertaken because regulatory burdens ensure there would be no profit for the developer. Personal gain for the regulator is thus to destroy the gains of people they will never meet, the exact opposite of what occurs in an open marketplace.