Katie Betzwieser / Intern
April 9, 2003
remember going through the profiles of researchers who were prospective
mentors for my upcoming internship for the fall 2001 semester. The
brief biographies that had pictures were the most interesting.
One person in particular caught my attention. Not because his research
sounded incredibly fascinating, but because he appeared laid back
and extremely cool: the exact antithesis of what I was expecting.
Grinning like he had just been caught with his hand in the cookie
jar, the biophysicist looked like an approachable, everyday Joe
who just happened to be doing some sort of research with the brain
it was Jonathan Haines’ affable appearance that influenced my decision
to work in his lab for a semester as part of my major in the Communication
of Science, Engineering and Technology. But it turned out to be
Haines’ research in neurodegenerative disorders, specifically Alzheimer’s
disease, that kept me intrigued and eager to learn as much as possible
about this devastating illness, its underlying causes and possible
Alzheimer’s is not only a disease, but also a story of destruction
by Dana Johnson
is not only a disease, but also a story of destruction and debilitation
of a human being’s most important organ. According to the National
Institute of Aging, four million Americans suffer from Alzheimer’s
disease, which progressively destroys the brain leaving a healthy
body with no control center. As Alzheimer’s slowly and gradually
takes over the brain, those afflicted begin to lose control over
daily functions such as memory, time and space orientation and communication
skills. Currently, there is no cure, but there is hope for the future.
Haines is a professor of molecular physiology and biophysics at
Vanderbilt, where he directs the program in human genetics. He is
also an investigator in the John F. Kennedy Center for Research
on Human Development. He wants to provide a happy ending to this
devastating story. He and his research team are looking at the genetics
underlying this affliction. Deciphering the genetic connection is
an essential first step toward finding effective treatments or,
even better, a cure. Their work is a small but vital part of all
the medical research currently being conducted to understand, treat
and cure this degenerative disease.
prepare myself for the internship, I read up on Alzheimer’s via
the Internet and the local library. Searching for a humanistic take
on the disease, I randomly chose a book, Hard to Forget: An Alzheimer’s
Story, by Charles Pierce. I was hooked after reading the first
few pages and did a double-take when I found that Haines was mentioned
in the introduction! How often do you get to work with someone who
is described in a book as one of the up-and-coming geniuses in his
a result, I was exceedingly excited to begin my work in the lab.
In early September, when Haines and I met to discuss the details
of my internship, we set up an introduction to the laboratory for
the following Tuesday, Sept. 11, 2001.
Lab routine disrupted by 9/11
by Neil Brake
Betzwieser in Haines lab
that fateful day, I walked to the Haines lab in a state of bewilderment,
trying to get a grasp on everything that was happening in New York
City after terrorists destroyed the landmark World Trade Center
Towers. Despite the horror everyone was feeling, Haines greeted
me with a kind smile, much like the one in his photograph. As we
walked to the lab, we talked about the events of the day, not once
thinking about Alzheimer’s disease or lab work. When we arrived,
we found life there revolving around the computer that the lab team
was using to find out as much information as they could about the
unprecedented terrorist attacks. We made quick introductions and
kept watching. Nothing else seemed as important, not even research.
After the visit was over, I realized that the experience had been
anything but stereotypical.
As I got to know the crew in the Haines lab, I found that they were
just as amicable as their boss. Kindness and smiles greeted me every
time I arrived. The graduate students, Holli Hutcheson and Shannon
Kenealy, were more than willing to help me with anything I requested.
The three research assistants – Krista Stanton, Shana Crabtree,
and Sarah Zika – were just as enthusiastic and encouraging. And
Brent Anderson always provided the bit of male humor needed for
a group of gossipy girls. Think of the movie “Office Space” set
in a lab, but without the bad boss and monotonous job. They were
the “hot-chicks-and-one” lab that the fourth floor of the research
building talked about because of their entertaining personalities
and happy dispositions. They were the ones who would contribute
to one of the most memorable and worthwhile experiences of my lifetime.
Think of the movie "Office Space"... without the bad
by Neil Brake
Betzwieser, below, with Krista Stanton, left, and Holli
I wanted to know about something, all I had to do was ask. I always
got plenty of answers. Not all the questions revolved around Alzheimer’s
disease or DNA or research in general. We talked about the things
that happened over the weekend and the interesting vendors who sold
paraphernalia to the lab. I can state unequivocally that there are
no stereotypical science “geeks” in the Haines’ lab.
lab works on many projects, but I focused my attention on the research
being done with Alzheimer’s because the disease affects such a great
number of Americans. Currently, Haines and his research team are
concentrating on mutations in genes located on chromosomes 10 and
12 as a possible cause for late-onset Alzheimer’s, the most common
form of the disease. The researchers begin with blood samples collected
from families whose medical histories show an unusually high incidence
of the disease. Then they look at the DNA isolated from the samples
for anomalies or mutations.
Laboratory divided into three parts
Research in the laboratory is divided into three sections: family
ascertainment, core lab and then statistical analysis.
The family ascertainment group gathers family history information
and collects blood samples from families that exhibit a high occurrence
of Alzheimer’s disease.
in the core lab isolate DNA from the blood and cut it into short
pieces so they can look for mutations in specific locations. In
the regions of interest, the lab workers compare the base pair
sequences in the DNA of normal individuals with that of Alzheimer’s
patients and their families.
Data generated in the family ascertainment group and the core
lab is sent to the data analysis group. Here, analysts determine
the statistical probability that a given gene mutation is implicated
by Neil Brake
Betzwieser working with DNA in Haines lab
spent most of my internship in the core lab where I worked with
beginner’s DNA to learn the basic steps of isolating and examining
this incredible molecule. Those steps are: PCR, gel electrophoresis,
and scanning for the necessary DNA fragments.
or polymerase chain reaction, is the process used to make large
amounts of DNA so that it can be studied and sequenced. The DNA
is mixed with primer molecules that attach to specific spots on
the DNA strands. A special enzyme, called DNA polymerase, causes
the two strands to separate in the region between two primers and
makes copies of that portion of the DNA. By repeating this process
30 to 35 times, millions of copies of the desired segment of DNA
are produced. This allows the researchers to look at particular
pieces of DNA in detail.
The next step is gel electrophoresis that separates replicated DNA
strands by size. It is based on the fact that when impelled by an
electrical force, shorter DNA fragments travel more rapidly through
a gel than longer ones.
Learning the basic techniques
To learn this technique, I began by making the gel, which looks
like a glass sandwich with translucent jelly. I treated the marker
from the PCR product with dye for easier loading into the gel. Loading
a gel with the samples is not easy. Patience, accuracy and precision
are a must to prevent mishaps and errors that force one to start
all over. With a bit of beginner’s luck, I had few problems, but
I saw that even experienced lab workers can have trouble. Next,
I hooked the gel mechanism up to a battery that produced the electrical
field that pushed the electrically charged DNA fragments down the
After the samples ran, I prepared the gel for analysis by adding
a nucleic acid stain called SYBERGOLD. The stain causes the DNA
to fluoresce under a special scanner known affectionately in the
lab as “The Hitachi.” The scanner is hooked to a computer that produces
an image of the fluorescence, which can be printed out for analysis.
The identity of an unknown fragment is determined by comparing its
position on the gel with the positions of known fragments.
the internship, I met with Haines periodically. In the first interviews,
we talked about what the lab was focusing on, what kind of progress
the group was making and how he thought his work would contribute
to the future. At first, I asked typical questions and got typical
answers. I realized that if I wanted to understand what makes Jonathan
Haines tick, I needed to delve deeper.
our interviews that smile – the same one as in the photograph –
put me at ease despite the fact I was dealing with a person with
so much professional respect. Nevertheless, I had trouble getting
beyond his public persona. Despite his genuine interest in helping
me, Haines guarded his personal life and this complicated my efforts
to understand the life of a research scientist. But I would come
to find out that the most difficult questions are the ones that
yield the most unique and invaluable answers.
As director of the Program in Human Genetics, Haines oversees what
goes on in the lab, writes grant proposals and ensures that the
lab is on track. The long hours of paper work and meetings that
characterize his job today is much different from what he did when
he started out as a laboratory statistical analyst, he said.
received his doctorate in genetics from the University of Minnesota
and then did his postdoctoral work at the Indiana University School
of Medicine in the department of medical genetics. He did his first
research on Alzheimer’s at Indiana but it was not his first experience
with the disease.
When he was about nine or ten years old, he remembers hearing that
his grandmother had been diagnosed with Alzheimer’s, but he was
not aware of the situation or the implications of the disease until
much later. He remembers his mother making many depressing, stressful
trips to visit her mother.
memories of Alzheimer’s effects
by Dana Johnson
vivid memory that Haines has of Alzheimer’s effects came from his
last visit with his grandmother when he was a young teenager. Family
members sat around the table discussing how to make the best of
an obviously grim situation. His grandmother did not participate
in the conversation. “She seemed clueless about what was going on
around her. She sat obliviously at the table, bringing her thumb
and forefinger to her mouth like she was drinking a cup of tea.
There was nothing in her hand, nothing on the table and nothing
was going to her mouth,” he recalled.
As he and his mother left, she turned to him and said, “Don’t ever
let me get like that.”
1995, Haines remembers being at another relative’s funeral and watching
his mother. She had difficulty keeping up a conversation and expressing
herself. Because of his sensitization to Alzheimer’s disease and
the symptoms, he knew what was coming. In May 2000, his mother was
diagnosed with Alzheimer’s and Haines’ own family became a possible candidate
for the ascertainment group in his lab.
Having seen the destruction of her own mother, Mrs. Haines has withdrawn
from her normal, active life. Her reaction to her condition has
been hard for Haines and his family to take because they don’t know
how to deal with such an emotional and sensitive situation, he said.
I asked Haines how this situation affected his work, he replied
that he keeps the prospective of his own risk in the back of his
mind and tries to focus on the bigger picture of his research. Rather
than worrying about something he cannot change, Haines chooses to
concentrate on his research; who it will help; when it will make
a difference and how much difference it could make for so many.
Haines smiles as he remarks that his research is important, but
it is only the first piece in the complex puzzle of what causes
Alzheimer’s and how to effectively treat and prevent it. There is
a gleam in his eye and enthusiasm in his voice as he talks about
his work and its potential benefits to mankind. His face takes on
a look that I immediately recognize. It is the same look that led
me to intern in the Haines’ lab in the first place.
Haines online bio and research description