exploring career options

Hans Bjornsson, MD, PhDAssistant Professor in Pediatrics and GeneticsDirector, Epigenetics and Chromatin ClinicMcKusick-Nathans Institute of Genetic MedicineJohns Hopkins School of MedicineWhile many geneticists work with patients or in research, Hans Bjornsson holds both an MD and a PhD, allowing him to work with the very patients for whom he’s trying to develop treatments—a benefi t that he says helps him to truly focus his eff orts in the lab.

Geneticist Interview by Amy Entwisle

How did you become interested in genetics?When I was young, I was really into math

and physics. I couldn’t quite see myself

in a career in math or physics, though.

I attended medical school in my home

country of Iceland. The summer before

my last year of medical school, I attended

a conference called the Short Course on

Medical and Experimental Mammalian

Genetics, which has been organized by

Johns Hopkins University and Jackson

Laboratory for 54 years now. After attend-

ing the conference, I was hooked on

genetics. There is something magical

about being able to advance knowledge

to help someone’s health. The human genome—the

mechanisms, the machineries, the way this is impacted

by evolution, and how certain things lead to disease—is

just fascinating.

What is epigenetics and how is it different from genetics?There’s a lot more to genetics than the sequence of

nucleic acids in the DNA that make up our genes. The

epigenome (literally “on top of” the genome) refers to

a whole suite of chemical modifications of genes that

do not alter the DNA sequence itself, but that control

gene expression. Epigenetic marks—and hence gene

expression itself—can be modified by environmental

conditions like diet and exposure to chemicals. This

layer of genetic control provides a way to up- or

down-regulate gene expression without altering the

DNA itself; it is thus a genetic modulation system that

can act quickly, not just over generations, but within

the life of an individual. Most epigenetic marks are

inherited. And just as mutations in the DNA sequence

can be acquired as a cell copies its DNA, changes in a

cell’s epigenetic marks can be acquired, although how

those errors occur isn’t as well understood. Scientists

do know that epigenetic alterations can be caused by

environmental changes. For instance, certain fertility

treatments have been associated with a higher risk of

epigenetic defects. In my work, I focus on Mendelian

disorders—those caused by a mutation in a single

gene—that have epigenetic consequences.

What does your work entail?I spend about 20 percent of my time in clinic, and the

other 80 percent in the lab. In the clinic, I see patients

referred to us because of a possible genetic disorder.

Our job is to come up with a diagnosis. It’s a bit like

solving a complex puzzle. Sometimes, based on the

examination, we might suspect a condition that we can

test for by sequencing a particular gene involved. We

can also use a broader screening approach known as

a SNP (single nucleotide polymorphisms) array to look

for deletions or duplications anywhere in the genome.

This allows us to find even unique deletions or dupli-

cations that have not been described previously. But to

be able to identify single nucleotide mutations, we use

whole genome sequencing or whole exome sequenc-

ing, which allows us to sequence all the exons—the

protein-coding parts of the genome. Then the difficulty

is finding which mutation is really causative.

Having a diagnosis allows us to predict problems

patients may encounter and be proactive in caring for

them. For example, I see patients who have Beckwith-

Wiedemann syndrome, which causes a very high risk

of certain tumors, including a type of kidney tumor. If

we can make that diagnosis, we can screen for those

tumors and find them earlier, and that can lead to

a better surgical outcome; instead of removing the

whole kidney, surgeons might be able to remove a

portion of it.

In my research, I study Kabuki syndrome, a

Mendelian disorder of the epigenetic machinery that

occurs once in every 30,000 births. These patients

have beautiful eyes that reminded the doctors who

first described the disease of the face painting in

Kabuki opera. In addition to distinct facial features,

38 imagine

exploring career options

they have an immune deficiency, and around

90 percent also have an intellectual disability.

I’m interested in exploring why some people

have normal intelligence while others don’t,

and whether we might be able to develop a

therapy that could help with intellectual dis-

ability, which would be very exciting.

What is the value of having both an MD and a PhD for your work?Interacting with patients as a clinician helps

me to be the best possible researcher that I

can be. Meeting patients regularly reminds me

why I wanted to do research, and it helps me

focus my efforts in the lab. And when I can ask

a question and answer it within my own lab,

that’s very gratifying.

What is the biggest challenge that you face in your work?On the research side, the challenge is always

raising money to do the research. On the clinical

side, it can be quite challenging to deliver certain

diagnoses, but that’s also very motivating, because

it makes me really want to develop therapies.

Do you anticipate changes in the fi eld of genetics in the near future?This is a very exciting time in genetics.

Technology has started to transform what we

can do. Soon everyone will be able to have

their genome sequenced, which will allow

us to individualize medicine. We’ll be able

to make earlier diagnoses, target therapies

to individual patients, and avoid side effects.

We’re about to have a revolution in genetics,

and we’re going to need a lot more geneticists.

But epigenetics is still in its infancy.

Currently, we don’t have many clinical tests

that allow a genome-wide assessment of

epigenetics, like we do for genetics, but I think

it’s going to happen. And I’m excited about our

new clinic. Being able to see a lot of patients

with epigenetic disorders will allow us to learn

something about their variability. We might get

some new insights. We might fi nd new condi-

tions that overlap with known conditions. And

unlike genetic mutations, epigenetic marks are

more fl exible, with some of them being put on

and removed every day, so I’m very interested

in exploring possible therapies that take

advantage of that fl exibility.

What qualities do you think are important to be successful in your fi eld?It’s a very long path, so you have to be persis-

tent and not give up easily. When things seem

difficult or someone tells you that you can’t do

something right away, you have to believe in

yourself. I think that’s the most important thing.

It’s good to be smart, too.

Do you have any advice for students who are interested in a career like yours? They should do math and science, of course,

but they should also look for opportunities

to explore their interests. Some summer

programs, for example, allow students to

experience the lab environment. Attending

conferences and working in a lab while I was

in medical school really motivated me to work

toward the next level. So explore your interests

in order to find something that’s inspiring to

you, and then go for that.

The human genome—the mechanisms, the machineries,

the way this is impacted by evolution, and how certain things

lead to disease—is just fascinating.

What geneticists doMedical geneticists screen for and diagnose genetic disorders. They perform diagnostic tests, interpret lab results, and interact with patients and their families. They may plan and conduct research, write grants and professional papers, and attend clinical and research conferences on tech-nological advances and current research fi ndings. Some also teach.

Where they workMedical geneticists work in academic medical centers or universities, hospitals, government agencies, and private industry.

Education requiredGeneticists can have a PhD, an MD, or both. Those with a PhD generally work in laboratories and have little patient contact, while those with a medical degree usually have more patient contact.

Salary rangeAccording to the American College of Medical Genetics, the 2011 median salary for medical geneticists holding a PhD was $130,000; however, salaries for those with both an MD and a PhD are signifi cantly higher and vary according to responsibilities.

For more informationThe American Society of Human Geneticswww.ashg.org/education/careers.shtml

Genetic Science Learning Centerhttp://learn.genetics.utah.edu/content/epigenetics

The McKusick-Nathans Epigenetics and Chromatin Clinichttps://igm.jhmi.edu/ecc-clinic-glossary

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