QUEST Community Science Blog Author: Dr. Barry Starr

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Better Eating Through Genetic Engineering

August 18th, 2008 by Dr. Barry Starr

Scientists have created a mouse that doesn’t get as fat on a high fat diet.

You read that right. In a new study out in Nature Neuroscience, scientists tinkered with a single gene in a mouse and made it less likely to get fat. Finally I can eat as many Double Stufs as I want without worrying about gaining weight. If scientists can turn what they’ve learned into a pill, that is.

How’d the researchers do it? By changing one part of the mouse’s brain, the hypothalamus. One of the hypothalamus’ many jobs is body weight regulation. So it was a logical place to start.

The scientists couldn’t go in with a wrecking ball and tear the hypothalamus apart. It is an important part of the brain with lots of different duties. They needed to something pretty subtle so the mice would survive but be thinner.

What they did was to keep certain cells in the hypothalamus from being able to release a neurotransmitter called GABA. This was enough to make a mouse better able to maintain a lower weight.

This study suggests that GABA’s normal job in the hypothalamus is to keep mice (and probably us) from burning too much energy. Makes sense in the wild. But is quite a pain in my cubicle.

Now, we can’t go changing human genes (at least not yet). But perhaps scientists can come up with a pill that will do the same thing. A pill that keeps AgRP neurons from releasing GABA in the hypothalamus.

This is as hard as it sounds. But now that scientists know what to do, pharmaceutical companies will be able to apply all of their firepower to solving this problem. Given the potential market, if anyone can find a medicine for restricting weight gain using this finding, they will.

Before I get too excited, though, I want to see what happens to these mice as they age. Burning calories makes free radicals which damages DNA which causes aging and can cause cancer. Perhaps burning more calories this way might generate more free radicals.

Of course even if it does, maybe we could just take the pills with cranberries or some other anti-oxidant. Or maybe Nabisco can make an Oreo laced with antioxidants…




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Obesity and the modern man

August 4th, 2008 by Dr. Barry Starr

Given today’s environment, it is surprising that there are still thin people around.When I was at Raging Waters water park this weekend, I was reminded yet again of the obesity epidemic in the U.S. Almost everyone there (myself included) was at the very least overweight.

The origins of this epidemic are pretty easy to spot– lots of food and less opportunity for exercise. And yet, not everyone in the U.S. is overweight. So why is one person fat and the next thin?

One big reason is genetics. A number of twin, family and adoption studies have found that somewhere between 45-60% of body mass index (BMI) comes from the genes we inherit. In other words, some people are more likely to be sucked into a Super-Sized meal because of their genes.

So how might genes affect someone’s chances of succumbing to the mountain of food now available? Lots of ways.

Some people burn energy more slowly than other people. These folks need to eat less to maintain their weight. Not an easy thing to do!

Some people take longer to realize they are full. Others get hungrier more quickly after eating. Still others need more sweets and fat to get enjoyment from their food.

The last example was addressed by a study last year. One of the reasons people eat is that they get a hit of dopamine when they do. The dopamine makes us feel good and once we get it, we feel less inclined to keep eating.

The study found that people with a certain version of the DRD2 gene needed more food to get enough dopamine to stop eating. So they ate more on average.

There are more and more studies finding gene variations just like this one. Finding these gene variations might be useful in creating new medicines to help people eat less by decreasing hunger, burning calories faster, etc.

Knowing about these gene variations might also help doctors identify who is at a greater risk for obesity. These folks can get early help in maintaining their optimal body weight.

Now none of this is an excuse for getting fat (although I wish it was). For the most part, genes that affect our BMI make maintaining a healthy weight harder, not impossible.

But what it also means is that the thin should be a bit nicer to the overweight. Recognize that it might be easier for the thin person to not overeat.

This is not to take away from the thin person’s accomplishment. In a world awash in high calorie foods and with work and play involving a lot of sitting, it takes will power not to become overweight. Just remember that it is easier for some people to be thin.

http://www.cdc.gov/nccdphp/dnpa/obesity/trend/maps/index.htm




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Surviving Chromosomal Rearrangements

July 21st, 2008 by Dr. Barry Starr

Mole voles do fine with one X and no Y
chromosome.

Last blog I talked about the Transcaucasian mole vole. This little burrowing mammal has lost its Y chromosome over time. Now both males and females have only a single X.

I focused on how scientists can’t yet figure out how there are any male mole voles running around. This week, I want to focus on what this means from an evolutionary perspective.

These little animals show that massive changes in chromosome structure can be tolerated and the species can do quite well. Even when the chromosomal change results in a significant increase in miscarriages.

About half of a mole vole’s fertilized eggs don’t survive to term. Why not? Because these embryos have either no or two copies of the X chromosome.

Most mammals have two copies of each of their chromosomes– one from mom and one from dad. At the end of meiosis, each chromosome copy ends up in a different sperm or egg. This is so that when an egg and a sperm combine, the new mammal has the right number of chromosomes.

Mole voles end up with half of their sperm or eggs with one X chromosome and the other half with no X chromosome. There is a 1 in 4 chance that a sperm without an X chromosome will fertilize an egg without an X chromosome. Since mammals need an X chromosome to survive, these fertilized eggs don’t make it to term.

There is also a 1 in 4 chance that a sperm with an X chromosome will fertilize an egg with an X chromosome. In most mammals, this would be OK– the fertilized egg would go on to become a female.

But this is fatal for mole voles. Most likely this is because these animals have a defective Xist gene. This gene’s job is to keep only one X chromosome on in any cell.

Whatever the reason, these mole voles deal fine with the fact that half their fertilized eggs do not make it to term. This means that chromosomal rearrangements and changes that affect fertility can be tolerated. At least in the mole vole.

This is important because one of the key differences between a chimpanzee and a human at the chromosome level is that humans have 46 chromosomes and chimpanzees have 48. Looking at the DNA we see that human chromosome 2 looks just like chimpanzee chromosomes 12 and 13 fused together.

Some people argue that this sort of rearrangement wouldn’t be successful because at an early transition stage from 48 to 46 chromosomes, half the fertilized eggs would not make it to term. These fertilized eggs would either be missing or have an extra chromosome. Just like the mole vole.

Here we have a mammalian example where this isn’t an issue. This little mole vole is doing quite fine thank you very much. As our ancestors most likely did too.




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Why no Y? Gender-bending Transcaucasian mole voles

July 7th, 2008 by Dr. Barry Starr

I’ve always been fascinated by weird animals. Especially those with out-of-the-ordinary genetics.

Transcaucasian mole vole. Image Courtesy of Heike HimmelreichOne of my favorites is a little burrowing mammal called a Transcaucasian mole vole. These guys live in the Caucasus Mountains of Armenia, Iran, Turkey, and Azerbaijan. There they are born, live, have babies and die. All without a Y chromosome.

This is really bizarre. In most mammals, two X chromosomes usually means that the animal is female and an X and a Y means the animal is male. All mole voles have a single X chromosome. So technically, there shouldn’t be any males running around. And yet, clearly, there are.

So what distinguishes a boy mole vole from a girl mole vole genetically? No one really knows.

In most mammals, the Y chromosome causes a fertilized egg to turn into a male because of the SRY gene. This gene starts a cascade of events that eventually results in a male.

One possibility would be if the SRY gene happened to move to another chromosome. There are certainly cases of this happening even in humans.

If this were the case, then maybe a different chromosome has the SRY gene in mole voles. Maybe there are versions of the gene that work and versions that don’t. Now we have a gene no different than an eye or hair color gene.

Good model but it isn’t true. Scientists have looked but it appears that these little guys don’t have an SRY gene. They make the male/female decision in a completely different way.

Most likely somewhere along the way a gene mutated so that it could now determine the sex of these mammals. When this happened, the loss of the Y didn’t matter much and so it was lost. The mole vole evolved into a Y-less mammal.

Of course, if any chromosome had to go it would be the Y. It has been under constant attack ever since it distinguished itself from the X chromosome 200 or 300 million years ago. It has gone from being one of the biggest chromosomes with 900-1400 genes to a bit of DNA with around 80 genes.

There are even active discussions about whether the Y is on a death spiral in all mammals. Soon we may all be mole voles. Or be gone. Some of my recent posts elsewhere on this topic:

Males going extinct?
Fish that change gender




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Posted in Biology, Physics | 1 Comment

Genetic Testing or Recreational Genomics?

June 23rd, 2008 by Dr. Barry Starr

Do you have a note from your doctor?

So much information, so little understandingOn June 9, the California Department of Public Health (CDPH) sent letters to 13 different direct-to-consumer genetic testing companies telling them that they were not in compliance with California laws and needed to stop providing testing. The two main issues appear to be:

1. The testing facilities were not licensed correctly.
2. The tests were ordered without the request or counsel of a doctor.

This seems to me to be the opening salvo in an upcoming war between the government and these companies about DNA testing. The government wants to protect the consumer from getting incorrect results and/or misinterpreting the results they get. The companies want to provide people with information about their own DNA. I have to say I am unsure where I stand on this one.

On the one hand, there are some companies out there selling snake oil. For example, anyone claiming that they can provide a set of nutritional products based on your genetic test results almost certainly should be shut down.

And I would guess that the CDPH is not going after purely recreational companies like those involved in ancestry. I can’t imagine why a doctor would order that kind of test. If these letters target ancestry companies, then whatever laws are involved should be changed.

There are also companies that comply with the current California laws. One of the most prominent is DNA Direct. This company follows all of the rules of the state, only offers well validated tests that are performed in a CLIA lab, and provides genetic counseling so people can understand the results they get.

But what about the companies between DNA Direct and ancestry testing services? Although we don’t know for sure, the CDPH seems to have targeted many newer companies that look at hundreds of thousands or even millions of DNA differences at once throughout a person’s DNA.

The three main companies that I know about that are in this gray region are Navigenics, 23andMe, and deCODEme. Navigenics is a different sort of beast from the other two in that it only provides information on DNA differences that have a well established link to a disease and they also provide genetic counseling. The other two can really be thought more of as recreational genomics at this point.

23andMe and deCODEme give a client all of their information and then tell the client what is known about each DNA difference. They offer ancestry, trait, and disease information bundled up in a single 1000 dollar test.

These companies count on the consumer being able to digest all of that data and recognize what is a strong and/or important correlation and what is not. This is the point where a group that includes the government, doctors, and many academics differ with these companies.

Once we make sure that the testing is done well, the question really boils down to whether or not the consumer can handle all of the information*. Can consumers interpret these kinds of results and know when to seek help and when not to?

The answer is that some can and some can’t. So how do we protect those who can’t but still allow people access to their own DNA? Or should we protect consumers at all from their own DNA information?

*There is also the stipulation about a doctor ordering the test but frankly I don’t get that one and am not sure it should be part of any consumer protection.

Copy of the letter from Wired Science




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Vaccines: One Small Risk for a Child, One Giant Benefit for Mankind

June 6th, 2008 by Dr. Barry Starr

You’re as likely to be struck by lightning
as to have a severe reaction to a vaccine.

I was reading an article in Time last week about parents not vaccinating their children. The story was about how this phenomenon is becoming more widespread.

These kinds of stories are weird to me because vaccines are pretty safe. The risk of an adverse side effect is incredibly small. For example, the risk for anaphylaxis from the Hepatitis B Virus vaccination is around 1 in 600,000. This is about the same risk as being struck by lightning (1 in 700,000).

Of course, the article wasn’t talking about known risks. Instead, it was referring to a hypothesized link between vaccines and autism.

People proposed this link when they noticed that cases of autism and the number of vaccinations were rising at the same time. Of course, just because two things happen to occur at the same time, this does not mean they are causally linked. For example, the increase in global temperature is not related to the decrease in the world’s populations of pirates (despite what the Pastafarians say).

So how could an increased number of vaccinations cause an increase in the number of cases of autism? I have seen two ideas put forth. The first is that thimerosal is to blame. The second is that there are so many vaccinations now that we are stressing out the body’s immune system. Most likely neither idea is valid.

Thimerosal is a mercury-based preservative that used to be used in vaccines. Even though there haven’t been any good studies on the effects of thimerosal on brain development, everyone knows mercury is bad for the brain. So the idea behind thimerosal makes some sense.

Back in 2001, vaccine manufacturers decided to eliminate thimerosal from their vaccines. We would predict, then, that cases of autism should go down significantly if thimerosal was linked to autism. They haven’t. In fact, in one California study, cases have continued to climb. So thimerosal is most likely not to blame.

Another point that has been made is that there are so many vaccines now that we are stressing out our bodies’ immune systems. Again, this concern is unfounded.

Vaccines are injections of viral proteins. Our bodies see the proteins and raise antibodies to them. Then when a virus invades, we have antibodies that recognize the virus and target it for destruction.

It is the number of viral proteins that matter in terms of taxing the body’s immune system and not the number of vaccinations. All of the current vaccines put together do not have as many viral proteins as the old smallpox vaccine (150 vs. 200). So the number of vaccines is unlikely to be the issue.

What all of this means is that vaccines are probably not responsible for the significant increase in the number of cases of autism. What is responsible? No one knows for sure.

It may be that the rise just comes from all of us recognizing the symptoms more. Or it could be due to some cause we don’t know about or understand.

What we do know is that vaccines save many lives. I assume no one wants to go back to the early 20th century when polio epidemics swept the country. For example, 2,500 cases of polio ended up at one Los Angeles hospital between May and November of 1934. And in 1952, the U.S. had 21,000 cases of paralytic polio.

We can prevent this sort of thing from happening by making sure everyone is vaccinated. And yet there are people who choose to hide behind the people who take the miniscule risk of getting vaccinated.

Is this a matter of free choice? Should parents be allowed to opt out of vaccinating their children even if it risks society at large?

One idea, I suppose, is to have people who choose not to be vaccinated to sign a waiver saying they accept full responsibility for their actions. In practice this would mean that health insurance and the government would not be responsible for their children’s health care bills if they become ill with one of the diseases they refused to be vaccinated against.

And if your infant, grandma, or immuno-suppressed cousin came down with a disease these folks refused to be vaccinated against, then you could sue the un-vaccinated for damages. The common good isn’t enough to encourage these folks. Perhaps threats to their pocketbook will be.




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Posted in Biology, Chemistry, Health, KQED, Partners | 8 Comments

Drive by Science is OK Too

May 27th, 2008 by Dr. Barry Starr

The author feeling cheekyLast Monday I finally took my show out on the road. At The Tech Museum I run hands on genetics programs for visitors. On Monday, we took them to Overfelt High School in San Jose.

And the students had a blast*. They got to take home 4X6 glossy pictures of their cheek cells like the one I posted here (that’s my handsome cell). They got to use DNA from a crime scene to solve a murder. They got to make bacteria glow like a jellyfish. They got to spool their own DNA. And they got to learn what 1000-2000 bases of their DNA looks like.

For the most part they were genuinely excited and engaged in the activities. They learned about nuclei, dominant and recessive gene versions, why blood cells look different from nerve cells and lots more.

Some educators call this sort of thing “drive-by science.” A scientist zooms in, wows the kids and then disappears. These educators feel that this sort of thing has little effect on learning science. I beg to differ.

This experience obviously can’t replace classroom learning. But it can reinforce what they’ve already learned. And it can show them how exciting science really is (even if their textbooks have convinced them otherwise).

Nice theory, but is there any proof this sort of thing works? You betcha.

A new study out by the National Academies shows that this kind of “informal learning” greatly increases the retention time of the things people learn while in that environment. For example, these kids, having seen and taken a picture home with them of their own nuclei, will remember that a nucleus houses DNA longer than if they learn it in a textbook or lecture.

If the study is right, the students will also become more excited about science so they’ll pursue it in the future. Especially if the teacher then does follow on activities to reinforce what they learned (which he will).

Hopefully the nine graduate students from Stanford’s Department of Genetics and I did our part to get some kids wanting to learn more about science. Maybe we even got a few to imagine themselves as scientists. Not bad for a day’s work.

* Quote from the students’ teacher:

These are some of the adjectives my students used to describe their experience: “awesome”, “cool”, “fun”; and they don’t use these very lightly when it comes to academic activities. Some of them were wondering if we are “going to do that again.” They enjoyed not only the activities, but also the experience of interacting with young graduate students from Stanford. Some experiences that can be a matter of fact for us can be huge for some of these kids and have a dramatic impact on their lives.






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Chromosome Fusion: Chance or Design?

May 12th, 2008 by Dr. Barry Starr

Human and chimpanzee chromosomes are very similar.
Note that human chromosome 2 is very similar to a
fusion of two chimpanzee chromosomes.

For the last few weeks I have been corresponding with someone about intelligent design (ID). More specifically, we have been chatting about why humans have 46 chromosomes and most of the great apes have 48.

To me, this is great evidence for evolution. Why? Because if you look at the chromosomes closely, you can see that human chromosome 2 is really just a fusion of two great ape chromosomes.

The idea is that a few million years ago, a common human-chimpanzee ancestor of ours had two of his or her chromosomes fused together. This sort of thing happens all the time even today. Around 1 in 1000 live births has one of these kinds of fusions.

Then, probably through chance,this ancestor with the fused chromosomes went on to found the human race. Now people have 46 chromosomes and chimpanzees have 48.

An alternative explanation is that the designers fused the two chromosomes together when they created humans. The idea would be that the designer wouldn’t create every plant, animal, bacteria, and virus from scratch–why reinvent the wheel every time? Instead the designers would mix and match parts that worked.

So as part of the process of designing a human, the designer fused two ape chromosomes together. This would presumably be simpler than creating a human chromosome 2 the way the other chromosomes were made.

The difficulty with this idea is that there is no obvious advantage to having 46 chromosomes instead of 48. What matters is our DNA, not how it happens to be packaged.

It is possible that there was some advantage to fusing the chromosomes together. For example, maybe a new gene was created at the fusion point. Or maybe genes that were shut off before were now turned on in the new fused chromosomes.

There isn’t any evidence of these kinds of things. And even if there were, a designer who can easily put in the 60 million or so differences between humans and chimpanzees should be able to accomplish whatever results a chromosome fusion gives more elegantly than sticking two ape chromosomes together.

Also, when you look at the fusion point, you can see that the DNA isn’t exactly what you would expect if a fusion happened in the last 10,000 or even 100,000 years. The results look more like an event that happened millions of years ago.

The ends of a chromosome have a defined sequence of DNA repeats called a telomere. The DNA at the fusion point looks very similar to a string of telomeres (as we would expect from a fusion) but it isn’t perfect. This is just what you would expect if the fusion happened millions of years ago. Because our DNA gets changed a little all of the time.

The environment or even our own cells can cause the wrong letter to end up in our DNA. Our cells are pretty good at fixing these mistakes but they don’t catch them all. What this means is that our DNA builds up mutations over time.

When an unfixed change happens in a sperm or egg, then it is passed down to the next generation. If the changes that aren’t fixed happen somewhere important, then they are selected for or against. But if they’re neutral, then they just build up over time. Scientists can even use these sorts of errors to predict how long ago something happened. Or to trace human migration patterns.

These DNA changes at the fusion point do not fit with ID if they don’t serve a purpose. Otherwise, why put them there? It will be interesting to see the results of experiments that might show if these sequences matter or not.

Dr. Barry Starr is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA.







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Posted in Biology, KQED, Partners | 49 Comments

Fish and SNPs: What fish are teaching us about human skin color

April 28th, 2008 by Dr. Barry Starr

These fish can tell us a lot about ourselves.

Species often end up a different color when their environment changes. And humans are no exception.

When people moved out of Africa tens of thousands of years ago, they were dark-skinned. Now when we look around Northern Europe or parts of Asia, we see much lighter people. What happened?

A common explanation has to do with sunlight and vitamin D. When people moved north, they got less sun. Less sun means less vitamin D and awful diseases like rickets.

Anyone who moved north and had lighter skin ended up getting more vitamin D and did better than their darker neighbors. After awhile, most of the population had light skin.

This is all well and good, but what happened at the gene level to cause this transformation? One way scientists are learning about how humans ended up with lighter skin is by studying fish. For example, the zebrafish has taught us a lot about why Europeans are often so pale.

The zebrafish is an important model system that scientists use to study vertebrate development, human disease, and lots of other things. A common mutant fish that scientists use in these studies is called “golden.” These fish have lighter, yellowish stripes instead of black ones.

Scientists discovered that these mutant fish had yellow stripes because of a single DNA difference (or SNP*) in their SLC24A5 gene. When fish have this DNA difference, they have yellow stripes.

These scientists next looked for this gene in people. What they found was that most of the people they looked at had two copies of the “black stripe” version of the gene. Except for Europeans. They tended to share a common SNP in their SLC24A5 gene that the scientists went on to show is a big part of why many Europeans have lighter skin.

Another group of researchers decided to dig a bit deeper and find out when this transformation happened. By looking at the DNA around SLC24A5, they found that lighter skin came to dominate Europe around 6,000-12,000 years ago. At first this result is a bit confusing because humans moved into Europe around 40,000 years ago. Why did it take so long for lighter skin to become the norm?

Scientists can’t know for sure but one idea is diet. Around this time, Europeans started to grow their own food. And a farmer’s diet has less vitamin D than does a hunter-gatherer’s diet. Maybe the lack of sun only started to affect Europeans after they started growing their own food. Then, after a relatively brief time, most Europeans ended up fair-skinned to get enough vitamin D.

This gene doesn’t explain all of skin color. For example, it doesn’t explain the difference in color between Northern and Southern Europeans. Or why some Asians have fair skin. But it does explain a good deal of European coloration. Thanks, zebrafish!

*SNP=single nucleotide polymorphism

Dr. Barry Starr is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA.





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Hug-a-helix: celebrate DNA Day, April 25th

April 14th, 2008 by Dr. Barry Starr

DNA magnified 850,000 times through a scanning electron
microscope
DNA day is coming up on Friday April 25th. This annual celebration of genetics and genomics was set up in 2003 to commemorate the sequencing of the human genome and the 50th anniversary of the solving of the structure of DNA.DNA day was thought of as an opportunity for teachers, students, and the general public to learn about DNA. And to have fun with it.

This should be a chance to pull DNA out of beef, strawberries, kumquats or even yourself and learn that you have around 100 billion miles* of DNA inside of you. In case you’re interested, that’ll reach from the Earth to Pluto and back when Pluto is farthest from Earth. And that is one person’s DNA.

Add up everyone’s DNA in the world and you get 125 million light years of DNA. (At least I think you do… these numbers are getting ridiculous!) That’ll get us to the galaxy Andromeda and back 25 times. Add up all the DNA on Earth and… OK, that’s probably enough of that.

There isn’t just a lot of the stuff but it is amazing to me how similar all human DNA is. The latest estimates are that people are around 99.5% the same at the DNA level. That means that all those light years of DNA are mostly the same old thing just copied over and over.

Notice the mostly. With 6 billion letters of code in every person, a 0.5% difference means 30 million differences between you and me. It is these differences that make me look different than you. And to a varying degree, make me act differently than you.

This code doesn’t work in a vacuum either. The environment can change how it works which is a big reason identical twins aren’t really identical. And one of the reasons why it is so hard to figure out the genetics of complicated diseases like diabetes or heart disease.

Our DNA also changes with time. Things in the environment might damage it. Or our own cells can make mistakes when they make copies of themselves. What this means is that today’s light years of human DNA will be different than the same stretched out DNA in 100 years.

This also means that you have some cells in your body have different DNA than the rest of your cells. And if a DNA change happens in sperm or egg cells, then they are passed on to the next generation. Which is where all the wonderful diversity around us originally came from.

As you can see, there is a lot about DNA to celebrate. It is huge and mysterious and we’re just starting to get a good grasp on what it is all about.

I plan to spend the morning of DNA day at The Tech Museum in San Jose exciting kids (and hopefully some adults) about DNA by running five different hands on genetics programs all at once. It’ll be a blast!

I have searched high and low for a list of DNA day activities here in the bay area but I haven’t come across any. Does anyone know about other DNA day celebrations here in the bay area?

* Each cell has 6 feet of DNA and we are made up of around 50-100 trillion cells.

Dr. Barry Starr is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA.






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