Retired university professors typically rest on their laurels after many years
of teaching and research and take it easy. Not so for Hebrew University
Faculty of Medicine emeritus professor Nathan Citri. Two decades after
his retirement, the veteran microbiology expert has developed a novel kit
enabling speedy detection of multidrugand extremely antibiotics-resistant
“superbugs” and providing instant guidelines for patients’ appropriate treatment
His invention will improve patient care, save lives,
shorten hospital stays and significantly reduce healthcare costs around the
world, according to Yissum, HU’s research and development company, which
recently signed a licensing agreement for commercializing the kits with
BioConnections, a microbiology company in the UK.
The Polish-born Citri,
who marks his 91st birthday this month, was in March one of 27 HU researchers to
be honored in a permanent photo exhibition on the Mount Scopus campus’s
“I hardly dealt with bacteria until the last two or
three years,” Citri told The Jerusalem Post
in an interview in his apartment in
Jerusalem’s retirement residence Nofim.
“Twenty years after I went on
pension, I became a microbe hunter,” he said with some irony. It was 80 years
ago that he first read the classic book Microbe Hunters by US microbiologist and
author Paul de Kruif – which remains a bestseller – which piqued his interest in
science and has remained high on lists of recommended science
After finding little interest in the kit idea among Israeli
pharmaceutical and medical supply companies, he went to London and met Prof.
David Livermore, an expert in medical microbiology at the University of East
Anglia who is also a senior authority on antibiotic resistance at England’s
Health Protection Agency. “He is the world’s opinion leader on this subject. He
immediately understood exactly what I was talking about,” said Citri. “He was on
his way from Japan to chair a conference on antibiotics resistance in the US and
we met when he stopped in London.” The deal with BioConnections was the
Today, antibiotics against streptococci or syphilis, for example,
still work, but not those against a growing number of bacteria.
antibiotic resistance, the microorganism is able to survive exposure to an
antibiotic. If people who have a viral infection unnecessarily take antibiotics
meant for fighting bacteria, or if antibiotics are otherwise overused, stronger
bacteria will evolve. As a spontaneous or induced genetic mutation in bacteria
may make them resistant to common antibiotics, genes that confer resistance can
be transferred between bacteria in a horizontal fashion by conjugation,
transduction or transformation. Exposure to antibiotics then selects for the
antibiotic resistant trait.
“Bacteria are the great survivors; humanity
is a short episode. We have to learn from them,” Citri warns.
pharmaceutical companies don’t find it financially worthwhile to develop new
antibiotics, doctors’ weapons against increasingly resistant bacteria have been
reduced, which could mean deaths. Thus the handful of most powerful antibiotics
that remain in the physicians’ armory have to be saved to fight the pathogens in
patients who really need them. That is exactly why Citri’s kit is such a boon.
“It will help prevent the spread of bacteria. In 15 minutes, the result shown by
my kit will tell doctors whether to isolate the patient and what antibiotics are
Using the conventional technology, doctors have to wait for
days to get an answer from the lab, during which the number of resistant
bacteria multiplies many times over.”
The World Health Organization
recently called on medical institutions around the world to stop giving
antibiotics when there was no evidence that they were needed and effective. In
fact, antibiotic resistance was the theme for World Health Day last
“When the first antibiotics were introduced in the 1940s, they were
hailed as ‘wonder drugs,’ the miracles of modern medicine,” said WHO
director-general Dr. Margaret Chan. “With hospitals now the hotbeds for highly
resistant pathogens, the world is on the brink of losing these miracle cures.
The speed with which these drugs are being lost far outpaces the development of
“In the US alone, antibiotic-resistant infections are
responsible for eight million additional hospital stays annually and for the
consequent bed-to-bed spread of resistance, taking a toll of $20 billion per
year in excess healthcare costs and $35 billion a year in societal
“But until my kits become widely available,” commented Citri,
“there is no way to implement this recommendation fast enough because the
physician doesn’t know whether using the antibiotic is justified or not.
Humanity is facing the end of the antibiotic era – and it’s our own fault!” The
unique identification kits are based on a chemical reaction that directly tests
for the presence of the antibiotic-destroying enzymes called beta-lactamases,
which are found in all multidrug-resistant bacteria. The kits enable direct and
precise recognition of bacterial resistance to all members of the beta-lactam
family, which include penicillins, cephalosporins and carbapenems.
kits are modular, disposable arrays of spots impregnated with several types of
antibiotics. The exact combination can be easily varied according to need.
Unprocessed samples of any specimen to be tested (such as blood or urine) are
placed directly on the array spots, which are then covered by a lid containing a
dark indicator dye. If the sample contains bacteria that can destroy the
antibiotic impregnated in a particular spot, the dark indicator dye facing that
spot becomes lighter, exposing the antibiotic resistance within
The modular kits will thus alert doctors to the presence of
multi-drug-resistant (MDR) or extremely drug-resistant (XDR) bacteria, warn which
antibiotics will be futile and indeed wrong to use and inform which, if any,
still constitute a treatment option. Thus, for the first time, evidence-based
guidance for appropriate treatment can be made available without delay.
Furthermore, treatment efficacy can be easily assessed by real-time
The kits not only detect the presence of bacteria resistant
to antibiotics, but also offer immediate information on the type of antibiotic
that may still be of use.
At present, antibiotic resistance assays used
in the lab are indirect and consume precious days of testing. Citri’s approach
of using enzyme identification kits enables a direct visualization of the
activity of betalactamase, the resistance conferring enzyme. The information on
the presence and activity spectrum of the enzyme is received within minutes, and
enables evidence- based treatment.
Ken Denton, CEO of BioConnections,
said: “We are very excited with this new partnership. The first kits are
in the last stages of development, and we hope it will reach the market within
months. In parallel, we have applied for a CE mark for marketing of the kits in
“We are pleased to collaborate with Bio- Connections for the
commercialization of this invention,” said Yissum CEO Yaacov Michlin.
“Drug-resistant gut bacteria present the most alarming, imminent threat to our
ability to control infectious diseases. In order to contain its spread, a case
of multidrug resistance should be promptly isolated and treated with the one or
two last-resort drugs that may still work. However, currently available
techniques for identifying drug-resistant bacteria are slow or hardly accessible,
and evidence-based decisions are delayed for days. Prof. Citri’s invention... is
an extremely important step in our fight against antibiotic resistance and one
that will not only greatly improve patient care, but will also save billions of
dollars in healthcare expenses related to antibiotic resistant
CITRI NEVER intended to become a scientist, but to be a farmer
in a kibbutz. It was the Holocaust – to which he lost most of his family – that
persuaded him otherwise.
He was born with the name Natan Cytrynowski on
April 21, 1921, in Lodz. His father, Yechiel, was a Hebraist, Zionist and
painter and worked as a Hebrew teacher in the Yavne private Hebrew coed high
school in the Polish city. Later he became principal of the school. Coming from
a hassidic family, Yechiel rebelled against haredi life and was the only member
of his family who became a Zionist. His Russian-born mother, Genia, taught
Hebrew language and literature in high schools for girls. Natan and his younger
sister Miriam were thus raised in a Hebrew-speaking home where Zionism and moving
to the Jewish homeland were pervasive ideas.
When a Youth Aliya emissary
arrived in Lodz in 1936 to rescue Jewish children, Natan insisted on going the
following year to Palestine, with the family planning to join him as soon as
possible. “I was the only one to survive. I owe everything to [Youth Aliya]
founder Henrietta Szold. Youth Aliya was one of the greatest accomplishments by
In 1939, Yechiel traveled to Palestine to look for work and
try to get entry for himself and his family. He was offered an excellent
position and went to bring his wife and daughter, but they did not make it out
of Europe in time.
As World War II broke out, the three moved to Warsaw,
where they were forced into the ghetto. Genia died in 1942; Yechiel was
transported to Treblinka, where he met his death; and Miriam, who slapped a Nazi
officer in Auschwitz, was shot by him and killed on the spot.
to study at Ben-Shemen (now-President Shimon Peres was two years younger and
“apparently doesn’t remember me”). Then he volunteered for the British Army in
1942 and remained until 1946.
“My father had drawn a scroll for the
opening of the Hebrew University back in the ’20s. I was less than four
years old when I saw him doing it. By accident, I pushed his finger,” Citri
recalled. The scroll was sent to Jerusalem for the opening. When Natan was an
IDF commander at Mount Scopus during the War of Independence, he found scrolls
on the floor of the shelled library. “I looked for his scroll and found it; I
identified it by the centerpiece – the dome of the library – and found the place
where I had pushed his finger. He hadn’t changed it.”
For a while
Citri kept his original name in the hope of being identified by Holocaust
survivor relatives, but then, when no one was found, he shortened
Finally out of uniform, Citri remembered the call of Labor Zionist
leader Berl Katznelson to fill the ranks of Jewish intellectuals lost in the
Holocaust. Instead of becoming a farmer, he decided to be an academic at the
Hebrew University. “But I lacked a matriculation certificate. Without it, I had
to be tested in eight subjects. I studied for weeks round the clock and passed.
I was accepted to study bacteriology, but studied general science and then
With his first wife, Citri had a son – “a
brilliant neurobiologist who was killed in 1995 in an accident,” and a daughter,
who is a social worker at Hadassah University Medical Center. His second wife,
Naomi, gave birth to a son, who is now completing work at Stanford University in
California and is coming to work at HU’s natural sciences faculty
Since Naomi died of illness last year, his book- and test-tube
filled apartment in Nofim is shared by Lorena, a Filipina
Citri has six granddaughters and three
He notes sadly that the children and grandchildren
of many in the elder residence live abroad. “In Israel, when I do something, I
can see the blessings. I can make a contribution. In the US, what I do
would not make a difference,” he concluded.