Tully is a professor of genetics at Cold Spring Harbor
Labs on Long Island, New York. A native of Washington,
IL, Tully attended the University of Illinois, where
he obtained a B.Sc. in both Biology and Psychology and
a Ph.D. in Genetics.
investigates the genetic basis of memory. His research
seeks to identify the genes involved in neural development
as well as neural function. The goal of his work is
to develop effective treatments for memory loss, both
behavioral and pharmacological. His experiments on "photographic
memory" in fruit flies was the first demonstration of
genetically enhanced memory in history.
lives in New York with his wife Nance and their two
sons, Benjamin and Schuyler. Tully also he has five
siblings and 26 first-cousins, from whom, he notes,
he gained an intuitive understanding of Mendelian inheritance.
links to this scientist's home page and other related infomation
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What can I currently do to improve my short/long term
"real" therapy (drug or behavioral) yet exists. Emerging
literature, primarily from cognitive psychologists however,
suggests that "brain exercise" may work to maintain
optimal functioning of working (one type of short-term)
generally, recent research suggests one MOST IMPORTANT
thing you can do to maintain cognitive vitality as you
age - exercise (!) Physical exercise works to promote
cognitive health in two ways. First, cardiovascular
fitness (low cholesterol and less artherosclerosis)
minimizes the chances of "mini-strokes." Modern brain
imaging studies have revealed a high incidence of these
clinically undiagnosed events. Presumably, they cause
small but cumulative damage to the brain, which eventually
results in memory loss. Second, physical exercise actually
produces increases in a brain chemical called, BDNF.
BDNF promotes neuronal survival and may protect against
the damaging effects (cell death) of stress. Combined,
these positive effects of physical exercise are 40 times
more important for cognitive health than any other known
A simple one, really...I thought your experimental design
was interesting! Just wondered if you varied the odors
that the flies were exposed to so that you made sure
the response wasn't related to the particular odors
you chose. Thanks!
we do. In a typical experiment, we actually train two
separate groups of flies. For the first group, odor
A is paired with footshock and odor B is not. We reverse
this relation for the second group; odor B is paired
with shock and odor A is not. The results from these
two group then are averaged to produce ONE "learning
index." Arithematic and control experiments have shown
that this method eliminates any small bias that the
flies may show to one odor versus another - and the
only way to obtain a learning index greater than zero
is if the flies learn to avoid the shock-paired odor.
Gretchen A. asks:
We watched your discussion with Alan Alda with great
interest, as our son, diagnosed with Asperger's disorder,
tests in the 2d percentile for short term memory, and
in the 98th percentile for long term memory. Might your
research into the CREB gene eventually serve to even
out this imbalance? There are also issues with being
unable to read social cues, which may also be due to
his short term memory deficits. We are interested in
whether your studies might be applicable to the early
years as well as the later.
we simply don't know whether our emergent drugs that
enhance the CREB pathway will help those diagnosed with
Asperger's disorder (and others). Further research may
establish one possibility, however, based on the following
speculation: Perhaps the primary function for the brain
is to be plastic - to perceive and process new experiences
and then to change its function in response to this
"knowledge." Brain plasticity is an ongoing process,
likely to persist in all regions of the brain. Relatively
mild genetic predispositions, exerting their effects
early in development, then might yield apparently large
defects in brain function - which nevertheless might
be altered toward normal function by intense brain exercises
focused on the particular cognitive dysfunction(s).
In this manner, it might be possible to reshape some
"heritable" cognitive disabilities. To this end, Scientific
Learning Corp. is developing training protocols for
several aspects of cognitive dysfunction.
Rosanne K. asks:
What an interesting segment. I am very much interested
in your work because my husband has a brain injury which
greatly affects his short term memory. Could this gene
help him someday with his memory? I'm just curious and
would love to follow your accomplishments- how can a
layman follow your work? Thank you for your time and
the work you are doing.
per explanations above and below, development of drugs
that target the CREB pathway may someday lead to beneficial
therapies for your husband. Some of the brain circuitry
that has not been damaged by the injury might be trained
to take on some of the function(s) lost in injured region.
As with stroke rehabilitation, however, such training-based
therapy requires a lot of intensive practice and often
does not result in a complete recovery of brain function.
We hope, at least, that CREB-enhancing drugs will reduce
the amount of practice required to reach the therapeutic
for your second question, you can follow scientific
progress by watching television programs like Scientific
American Frontiers and by keeping an eye out in the
popular press, such a newspapers and science magazines.
Though our work is slow and often esoteric, I consider
it important to try to communicate the essence of what
we do to others. My mother always used to say, "Just
tell me about your work in a way that I can understand."
I've taken that loving advice as a challenge.
Lance M. asks:
You said something about taking certain medicines in
the future which will cause memories to be stored as
long-term. Could this extra long-term information cause
the brain to overload? Thank you very much.
if the drug is strong and is taken for a long period
of time (see above). That's why it may be best to use
such drugs acutely -- in combination with deliberate
and specific brain exercises.
Marilyn P. asks:
Do you have a theory on what the gene therapy is doing
inside the brain? Is there any change in the amount
of any specific neurotransmitter being produced in the
brain? In the human brain, would you expect changes
to be happening in the hippocampus?
far, we only have a crude theory of what is going on.
There's reasonable evidence for changes in synaptic
structure during long-term memory formation, but little
evidence yet exists to implicate specific molecules.
These are the experiments that several of us now are
working on. Genetic experiments in rats clearly have
shown that CREB functions in the hippocampus during
long-term memory formation. It follows, then, that drugs
which enhance the CREB pathway also will enhance hippocampal-dependent
long-term memory formation, if they reach that part
of the brain.
Rob Reiner asks:
1) Is there anything that is currently available for
humans that will help long-term memory?
2) If not, what types of treatments do you foresee being
available for humans (i.e. pharmacological, genetic
therapy, etc.)? What time frame do you foresee them
being available to humans?
3) Do you have any suggestions for how I could improve
my long-term memory today? 4) As a layman interested
in memory research, I sometimes find it difficult to
find new relevant information on the subject matter.
Besides Scientic American, can you suggest any publications?
Thanks for your time (and your research breakthroughs!)
P.S. I look forward to hearing about your next breakthrough!
The bona fide cognitive enhancers currently available
are those marketed for the treatment of Alzhiemer's
diseases. These all are cholinesterase inhibitors, which
act to elevate levels of the neurotransmitter, acetylcholine.
Higher levels of acetylcholine increase "attentional"
processes, including working memory. Better working
memory, then, helps indirectly to improve long-term
In the near future, I anticipate the development of
traditional pharmaceutical treatments for long-term
memory loss. A few lead compounds currently are being
identified. Given the (wise) FDA approval process, the
first of these may be ready for use sometime in the
next ten years. I do not foresee viable gene therapies
for long-term memory loss in the near future. The techniques
necessary to deliver such genetic constructs to specific
regions of the brain simply do not yet exist.
Brain exercise!! If you don't use it, you'll lose it.
From studies of the prevalence of Alzhiemer's disease
emerged the puzzling statistic that people with a higher
level of academic achievement appear somewhat less suseptable.
Researchers believe that this may occur because (i)
those with more schooling have learned how to exercise
their mind and (ii) a lifestyle of more exercise has
produced a "reserve capacity" in these people against
which neurodegeneration must act longer before memory
loss becomes apparent (and see answer to #1 above).
That's difficult. Of late, I've been impressed by the
amount of reasonable, intelligible information that
can be found on the Web.
Do you have any suggestions for repairing neurological
damage that affects memory? We're assuming that my daughter's
memory problems stem from a bout of RSV, during which
her brain was oxygen deprived.
second question: What can we do to improve our own memories?
Will there be gene therapy available for humans soon?
My own memory has been blipping in and out. Doctors
assume that it is due to constant stress. I've heard
that cortisol exposure affects memory. Thank you for
a fascinating glimpse of your work.
exercise," as discussed herein, might work for your
daughter - and is analogous to the usual rehabilitative
therapies after stroke. Unfortunately, however, such
therapy cannot repair all of the damage from injury
and, consequently, does not often yield a full recovery
of function. In any case, don't give up! The brain is
far more plastic than we previously were inclined to
your second question: brain exercise, physical exercise,
etc. (see above) all improve memory. Gene therapy: hope
not; traditional drug therapy is more reasonable and
more likely to become available in the next decade.
Stress: Yes, stress has a negative effect on memory.
Some studies, in fact, have shown that stress promotes
neuronal death in the hippocampus - that part of your
brain involved with conscious (declarative) memory.
Here again, however, physical exercise can help to reduce
and manage stress. That's why I put a treadmill in front
of my television!!
Why does the mind forget? Wouldn't it best serve an
organism to remember every experience and lesson it
is exposed to? Does the fading of memory have some purpose
for the brain? Thanks!
one knows for sure - but we certainly can speculate.
In spite of the fact that the human brain contains perhaps
as many as 70 trillion synaptic connections, this still
represents a finite number. Given enough time (and now
we live almost twice as long as evolution normally has
allowed) and experience (we live in an information age),
we nevertheless might "fill the hard drive." Hence,
the CREB switch might have evolved to function as an
"information filter" for most circuits in the brain.
Exposure to one experience on a single day may not be
sufficient to activate the switch and induce long-term
memory formation, thereby preserving some synaptic connections
for more important (recurrent) events.
studies of people born with truly exceptional idetic
memories seem to support this notion. Such people show
extraordinary memory capabilities. The famous Sherenshevski,
for instance, once was asked to memorize a complex mathematical
formula, in which the psychologist deliberately had
place an error. After a day of practice, Sherenshevski
was able to recall the formula perfectly (with the error
in it) more than 15 years later!. In spite of this memory
capacity, Sherenshevski could not remember two separate
conversations with the same person. Consequently, his
social skills were seriously impaired, and he could
not hold a steady job. These observations suggest that
having too much long-term memory may not be a good thing.
But, another important interpretation current exists.
Perhaps, Sherenshevski's disabilities were developmental
and not directly due to his enhanced memory. Only further
research will distinguish these alternatives.
Dale K asks:
You mentioned that fruit flies had an optimum time period
between "lessons" that worked best for long term memory.
(I believe it was 15 min.). As a musician who would
like to memorize as efficiently as possible, I am interested
in what the optimum period would be for humans. Has
this been worked out?
"It" has not been worked out. More to the point, there
may be different optima for different types of tasks
(sensory modalities). This notion of a rest interval
for spaced training applies to the cellular process
of long-term memory formation - and the underlying changes
in synaptic structure. Some evidence from higher vertebrates
also suggests a circuit-level process of memory formation.
With declarative tasks, for instance, (protein synthesis-dependent)
memory is dependent on hippocampal function for the
first two-to-four weeks. Afterwards, however, declarative
memory is intact even if the hippocampus is surgically
removed! These and related studies suggest that one
circuit-level function of the hippocampus is to "transfer"
LTM to other cortical regions of the brain. A different
line of experimentation has revealed another circuit-level
phenomenon. Work on rats and even on humans has shown
that preventing the subject from entering deep-wave
sleep will eliminate any increase in long-term memory
produced by spaced training. Research on rats implanted
with multiple electrodes in the hippocampus suggests
why this might be: Shortly after learning a new experience,
researchers detect an organized pattern of neuronly
activity in the hippocampus. This same firing pattern
then reappears during deep-wave sleep!
My interpretation of these observations is that higher
vertebrates have evolved a "play back circuit," which
is used to provide implicit spaced training to drive
the cellular process of long-term memory formation.
Lower organisms that don't possess this circuitry, must
receive explicit, spaced repetitions of an experience
to drive the same cellular process.