Chapter 3

 

Coming to America

I returned to Pakistan as a changed person!  My ideas of science, religion and human being had reformed and matured. Since, this account of my life is about my academic life I will not go any further about other issues.

I began to attend Karachi University where I earned a bachelor in Microbiology and a master’ degree in Biochemistry.  I wanted to get even higher education, but in Pakistan at that time, that was as high as I could get.  So, in 1972, I flew to Chicago’s O’Hare airport—carrying just a suitcase of clothing and small amount of money in my pocket. I have learned to survive without any money when I was an ascetic so this shortage of money was not so scary for me at all.  And, in the US, it was easy to survive and gain knowledge.  So, next is my summarized version of my academic quest.

I didn’t know anyone in the U.S., but in 1972 finding employment was a very easy event. It was so easy to get a social security card in those days. One has to go to the SS office and show the passport and the clerk will type up the card right in front of you and here it was.

It took only few days for me to get to SS office and get my card.  Initially, I found shelter with some students whom I met during my flight from London to Chicago.  They were kind enough to have me for couple of weeks with $50/week.  I immediately found work in the road construction industry and then in a foundry that manufactured screws and nails and bolts.  I learned to drive a forklift and worked in the night shift. I earned #3.65/hr and worked 50-60 hours/week.

It was very cold in Chicago, so three months later I moved to Fort Wayne Indiana.  There, I got better job- manufacturing brake shoes for the Ford Motor supplier in Albion, Indiana, near Ft. Wayne. I also started to take few courses at a nearby college, St. Frances College, so I can pick up skills how to get educated in the USA.  I saved my wages and after 18 months, I enrolled at the Indiana University in Bloomington.  Here, I took undergrad courses in microbiology and worked fulltime in a nearby hospital’s clinical laboratory.  They gave me intense 6-week training in all areas of the clinical lab.  Therefore, I moved from Bloomington, IN. to Martinsville, IN and worked day shift and took night calls every other night.  Until this stage, I have learned how to study in the US education system and that how rigorous it was. Now, the question was what to major in?  Going to Med school was not the option since getting into Med School was impossible in the US for someone who was educated in a foreign country like me and it was extremely expensive.  I had no intention to earn another 4-year college degree in Biology to qualify for competing for Med School!  Since, I already had a Master’s in Biochemistry!  So, after careful analyses I decided to apply for a Ph.D. program in Indiana as well as few nearby states.  I liked Midwest and felt like home.  Therefore, in 1974 I got into the University of Louisville’s microbiology/immunology graduate program.  However, there were no scholarships for foreign students like me. However, I was used to working and leaning all my life so soon I got a job working as a medical technician at the nearby Clark County Memorial Hospital in Jeffersonville, Indiana.  My ability to carry out blood sample analyses in hematology, chemistry and microbiology made me a good asset.  In the evening shift only two med tech worked and it was necessary that were skilled in a broad areas of clinical lab methods. In addition to running various tests, we also ran EKG machines, and drew blood samples from every kind of patients, including from ER patients. In late 1976, I met a young nurse, Theresa Mahoney, and we were married in mid-1977.  By December of 1979, I had earned a Ph.D. in microbiology and immunology and in the same month our first child was born-Alex.

During my grad school I worked on cellular immunology using African sleeping sickness, which is a major menace for herd animals and humans in West Africa.  In those days cellular immunology was an up and coming field of biological sciences.  I had two very good mentors –John Wallace and John Mansfield.  Dr. Wallace was the chair and the direct academic advisor to many of us and Dr. Mansfield was my research advisor, whose lab I worked in.  Initially, my project was to determine the roles of various T-cell subsets in mice infected with a deadly strain of African Trypanomiasis called EATRO-1886.  In those days, the exact nature or biomarkers for T-suppressor cells, T-helper cells and idiotypes feedback network was still not well defined and we had to rely on various kinds of antigens to figure out the possible mechanisms.  In the Mansfield lab where were few former grad students had unsuccessfully attempted to set up a plaque forming assay from the splenic lymphocytes for pneumococcal polysaccharides.  I was able to do this within weeks after my arrival to his lab and in less than a year we had a publication in the Journal of Immunology.  In reality, my doctoral project was done, but I was given another project to complete and that took me several years to complete.  By 4 PM I was usually done and leave for work at the hospital.  I would work until close to midnight and then drive home.  I will go to sleep and wake up around 7 AM, have few crackers and tea and go over my schedule for the day and start the cycle.  I would work 7-day a week and I still do!

Throughout my doctoral studies, I worked fulltime at the hospital lab while working fulltime at a grad student.  I will come to the school and take courses as well as carry out my planned experiments that generally required injecting 100 or so mice with the deadly parasite intraperitoneally or via the tail vein and bleeding the mice which were infected previously from the tail vein almost daily and then measuring their parasitemia on glass slides.  I was very organized and multi-tusker.

A month after my graduation, I joined a group in Albany, NY to do my post-doctoral fellowship in Infectious Diseases.  Here, I worked on more refined version of humoral and cellular immunology on Syrian hamster infected with syphilis Treponema pallidum (Bosnis strain).  This was a very good model of human syphilis and subsequently, I developed a model of congenital syphilis, which is the only animal model that mimics human congenital syphilis.

In 1981 we moved to Philadelphia, when my post-doc mentor moved to the city, where I received my first junior faculty appointment at Hahnemann University and in the same year I became a citizen of the United States of America and our second child was born-Anisah. After arriving at Hahnemann, I wanted to work on a separate project that was from my own thinking and I discussed my intention but not the idea with my advisor.  He appeared very glad and told me that he will support in my efforts.  So, I would stay after 5 PM and started to write a small proposal that was related to development of a vaccine against African sleeping sickness. The parasite changes its surface antigen once week or so and every time the host mounts an immune response the parasite changes its surface antigen and this cycle goes on until the host immune system is exhausted and host succumb to the infection.  My idea was to isolate the backbone antigens and immunize the host with that antigen and prevent the diseases altogether.  I submitted the proposal for an internal panel to provide me seed money to start the project before I can submit a RO1, the most elite form of award -a large NIH proposal. I was funded right away.  My mentor was working under the Chief of Infectious Diseases who also moved to Hahnemann when we moved as a team.  Well! When he discovered this funding news and he went ballistic!  He came to the lab and cursed me out with four letter words.  He used religious and racial slurs.  My direct mentor was silent and that event took place while he was present.  I was very upset!  I had developed very good relations with the chair of Pathology and Laboratory Medicine, Emanuel Rubin.  I made an appointment with him and spoke to him about my predicament.  He immediately called one of his top physician/scientist and introduced me to him.  This individual was from Yugoslavia and had received several RO1 grants.  He was looking for a lab supervisor for his very large group of grad and post doc fellows.  I was hired on the spot.  Next day, I packed up my stuff and moved to the new lab.  My only condition was that I would be allowed to work on my own projects besides working on his.  Dr. Rubin my new boss (from Yugoslavia) and we had a gentleman’s’ agreement that I will be allowed to work on my own ideas as an independent scientist besides supervising his grad students and post docs.

As soon as I arrived in the new lab, I began to manage at least 12 different projects on teratocarcinoma, which was the main focus of the group.  This PI was a world renowned immunopathologist and had published over 200 papers on everything! I induced immunology angle into some of the projects and developed many new ideas.  Within two years we published ten articles and I was able to submit a new proposal to NIH on congenital syphilis and I received my 1st RO1 award. Unfortunately, my new boss/colleague from Yugoslavia was manic/depressive and during his depressive phase would abuse everyone-all the grad students and sometime me.  I understood his illness since my whole mother’s side was suffering from similar illness.

After, I received my 1st RO1 award, Dr. Rubin-the chair of Pathology and Laboratory Medicine-offered me my own lab and support to further my academic career.  That was an utter surprise to me.  That did not set well with my Yugoslavian boss and several days later, when he was in his depressive phase, came and started to scream at me in front of the students and asked me to leave his lab.  That was really disheartening.  I really respected him and wanted in remain in the position as a lab manager.  The event immediately went to Dr. Rubins’ attention, since one the grad students, who was working under supervision on morphometric was Dr. Rubin’s grad student.  Dr. Rubin immediately arranged for a lab and office for me and I moved in to the new location the same day.  My new lab was twice the size of my Yugoslavian boss’s lab and I even had three offices in the lab.  But, I was distraught and did not like the events.  I realized that jealousy is a powerful force within man and it needs great deal of inner generosity in human to control the anger that arises from the successes of other fellow human beings.  In both cases, whenever I received a funding my bosses showed a great degree of anger towards me. The stories in the Holy Scriptures about Abel and Cain and the seven brothers of Joseph are examples for us to control these weaknesses! This was now time for a new direction and deep reflection! I reasoned that I still wanted to be a vaccine scientist like Salk, Sabin and Koch and all of them were primarily MDs but did not necessarily practiced medicine but used their knowledge of diseases to cure the disease.  So, going to Medical school was a good strategy for what I always wanted and for the job security for my family. I needed this knowledge to be what I always dreamed about.

This was second blow to my self-esteem and my years of hard work.  All through my career I treated my students, colleges and co-workers with utmost respect and care.  Going to Med school in the US was still an impossible task.  The admission for folks like me was almost not attainable and the tuition was outrageous.  I looked at a program in Mexico that was designed for Ph.Ds. and other professionals that required exempting from the basic science courses by taking a national test designed for folks like me-called MSKP (Medical School Knowledge Profile) test and it allowed you to exempt one from the first two years of medical school basic sciences courses.  I had taken almost all the basic science courses with the Med Students while I was a grad student.  So, I began to prepare for the test and applied at the UAJ, the Med school in Juarez, MX. After few months I flew to Juarez and took the test. I did want anyone to know except my wife what I was up to.  After few weeks the results came in and I passed.  I was one of the 28 applicants who passed (out of 231 applicants).  Then, I went to see Dr. Rubin and explained to him what I plan to do.  My idea was to resign and return the NIH RO1 award. He said “No”.  “He will find a better way.”  So, he asked me to come back tomorrow morning and he toured off my resignation letter and threw it in the waste basket.  Next morning, I got to work at around 7 AM to further ponder on the alternate and curious about what Dr. Rubin had planned.  Around 8 AM he walked into my office and asked me to come to his office.  After he sat down, he said, he asked me all about the program in Mexico, so I explained to him.  Then, he smiled and said in reality, you do not have to be in Mexico the 2nd year (the 4th Clinical year) and he can arrange for the clinical rotations for me in Philadelphia. Therefore, I have to be there to complete the mandatory requirements but 2nd I (that would be your 4th year in reality) you come back and he will arrange the requirements for the clinical rotations in the city.  I will be on leave of absence and he will call the NIH program director to arrange for a one-year deferment for my award.  So, here it was!  Among all the scholars in the world, Emanuel Rubin was a great man and he respected me and understood me!  I left for the Med School in March 1983 and returned in Oct 1984 (I had completed equivalent of 3 semesters of clinical studies in UAJ) and technically 4 semesters of basic sciences.  I needed 3 more clinical semesters in the US hospitals (the highest numbers of semesters required by the most stringent Med School is 10 semesters).

Upon my return, I juggled several balls.  I set up my lab and the Syrian hamster animal colonies for the research and while went through numerous clinical rotations.  First, I have to carry out a clerkship was for three months in Internal Medicine at Episcopal Hospital.  Dr. David Schlosberg was the chair of internal medicine then. My duty, as of any medical student who is doing internship, was to carry out History and Physical (H & P) on all new admissions. After few weeks he called me in his office, I was scared.  I thought I messed up someone’s H & P, his chief resident and two other senior residents were in his office.  He showed me my H & P report of a patient that I had taken few nights ago while I was on night call.  He said, this is the best H & P and most thorough he has ever seen it should be used as an example.  This is the first time I met him. And he first time came to know that I have a Ph.D. in Microbiology/Immunology.  So, he asked me if would be interested in a part time position to teach micro/Immunology to his staff and resident.  I came to know that he was board certified in Infectious Diseases.  I had to decline, but I felt very grateful.  He told the other residents to treat me like a resident not as a med student. I knew I had to work on my funded project.  So, I will go to Hahnemann after my daily internship hours (for foreign med students they called clerkship to distinguish between foreign Vs the US students), when my rotations were done. I hired a post-doctoral fellow who was a MD and a Ph.D candidate who would work on the project.  The graduate student was from Egypt and had an MD degree and was working on USMLE exam. Both of would start around noon and stay until 9 PM so I can supervise them. I continued on this double take for several years. During the 5th week of my rotation I heard the terrible news that my father has passed away after suffering from a massive MI.  I could not go to Bangladesh where he had died since in the Muslim tradition a person is buried within few hour after the death. I only could grieve for him at home.

My second rotation was at the St. Christopher’s Hospital for Children.  Here, I met The Head of the pediatric Immunology section-Dr. Harold W. Lischner, a world renowned immunologist and co-discoverer of DiGeorge Syndrome.  He already had read my articles and was aware that I had a Ph.D. in immunology and have a RO1 award.  I was totally surprised that he knew lot about me and wondered who told him.  He treated me with utmost respect and provided me personal training in clinical Immunology.  Harold was very thorough and very critical of his residents and fellows and he was considered a difficult person to deal with.  In my case I found him to be highly respectful and kind and a great teacher.  During my fellowship, I essentially spent lots of time in the Clinical Immunology Laboratory at the St. Christopher’s Hospital.

After a year, in 1985, I took the USMLE (used to be called FMGEMS) and passed both parts. I was officially a MD now.  After that Dr. Rubin advised me to do a one-year residency in anatomic pathology so I can be a licensed physician.  In those days only one year residency was needed to be a fully licensed physician. Meanwhile, I began a project on HIV.  I had been carrying on autopsies on the newly discovered menace AIDS.  Almost twice a week we will get dead folks who have died from AIDS.  I have requested that I would like to carry out the autopsies on all the AIDS bodies.  It was a great relief to other residents who were scared to death of performing autopsy on the AIDS cases.  I was collecting data and documenting and thinking about HIV and AIDS. From the clinical histories of the AIDS patients who died I concluded that in those days the majority of the folks who have died from AIDS were alcoholics and abused cocaine and other narcotics.

After my one year residency in Pathology Dr. Lischner asked me to join a fellowship program with him to work with the HIV/AIDS children. So, again, I worked as a fellow during 1986-87 and also worked on my grant research at Hahnemann in the evenings.  During late 1986 I  submitted a grant proposal to NIH in  on role of alcohol in development of AIDS.  I received my 2nd RO1 award in late 1987.

During 1986 I first became aware of invention of PCR or polymerase chain reaction. I acquired all the necessary reagents to work on the method. In those days there was no automatic thermocyclers available and Taq enzyme was not available yet.  So, I started to learn molecular biology and cloning methods.  I started to take workshops in Bethesda at the Life Technology, Inc. I initiated PCR experiments by using regular polymerase enzymes that required adding a one microliter of polymerase at the beginning of each cycle.  That was a long arduous experiment that took several hours with full attention, since one has to move a tube every minute from various incubators at different temperatures to complete each PCR cycle, manually. After thermocyclers and Taq polymerase arrived in market I envisioned developing a method where a gene of interest can be amplified inside the cell – 0n a pathology glass slide.  I figured this would replace the immunohistochemistry methods and would be more precise.  But, with my fellowship, RO1 research and other responsibilities, it was hard.  I needed a quiet time to work on this new idea. I thought of finding a place where I can carry out my funded research and just concentrate on developing the in situ PCR methods to amplify genes inside a cell. I began to apply at nearby university for jobs.

At the end of 1987 when I was completing my fellowship in Clinical Laboratory Immunology, I received a phone call from the Dean of a nearby Medical School in New Jersey (UMDNJ-SOM).  He explained to me that in South Jersey there will be a new medical school which will start in 3 or 4 years from now but all the state appropriations had been completed and he was recruiting new faculty. He also said a magic word-it was tenure track position.  Until now, Hahnemann was a non-tenure track University.  I have close to 20 publications and was PI in two RO1 and few small other grants.  I went for an interview and met the President of the University and few faculty members in Rahway, NJ. They offered me an Associate Professor position with 50% increase in my salary.  I would be located in South Jersey.  The new school would be eventually located only three miles from where I lived.  It was no brainer!  I went to see Dr. Rubin and told him about the offer.  He asked me to stay with him and revealed to me that he will be moving to Jefferson Medical College next month and wanted me to go with him.  I asked him if my new position would be tenure-track and he replied no.  He could not offer that.  I had no choice; I decided to go to UMDNJ.  I figured it would give me few more years to concentrate on In Situ PCR project.  During this period I submitted two more RO1s and one came very close to getting funded.  I received score of 122 and that year the last grant funded was 121.  I concentrated on the new method and began to develop a method where I could amplify HIV genes in white blood cells as well as in human sperms.  It took me almost three years before I published a small article in 1990 on the method.  I also developed collaborations with a thermocyclers manufacturing company – MJ Research – in Boston, MA, to invent a machine that could accommodate slides to amplify genes in situ on pathology specimens. Unstill that invention I was using the top of the standard thermocyclers and would place an aluminum fold and lay glass slide on the top and then put an insulated weight on it, so the heat would not escape.

During this period Dr. Lischner invited me to join him as an Associate Director of the Pediatric Immunology Clinic at the St. Christopher’s Hospital for Children.  The hospital was newly built and the facilities were state of the art.  I started to commute to Philadelphia and began to carry out the clinical laboratory immunology tests.  During this period I suffered my first major episode of severe depression.  As a physician I always knew that sooner or later this will happen.  I began to reflect on things and realize I need to be in a research lab doing my own things instead of running a clinical lab tests. That was not my goal!  I wanted to be a vaccinologist not a lab worker!

Therefore, in January 1991, I joined a lab at Thomas Jefferson University to work on HIV vaccine.